Clever Geek Handbook
📜 ⬆️ ⬇️

5′-untranslated area

The structure of 5'-NTO eukaryotes

5′- untranslated region (5′-UTR, pronounced as a five-bar untranslated region , English 5′-untranslated region, 5′-UTR ), or leader sequence [1] - non-coding region of mRNA located immediately after the cap , but before the coding region. The DNA section corresponding to the 5′-UTR of the transcript has the same name [2] . In the 5′-NTO, there are various elements involved in the regulation of translation efficiency [3] .

Structure

Length and nucleotide composition

The total length of 5′-UTR is approximately the same among all taxonomic groups of eukaryotes and ranges from about 100 to 200 nucleotides , but can reach several thousand [4] [5] . Thus, in Schizosaccharomyces pombe yeast, the length of 5′-UTR in the ste11 transcript is 2273 nucleotides [6] ) [7] . The average length of 5′-NTO in humans is about 210 nucleotides (at the same time, the average length of 3′-NTO is 800 nucleotides [8] ). The longest known human 5′-NTO is the Tre oncogene , its length is 2858 nucleotides, and the length of the shortest human 5′-NTO is 18 nucleotides [1] .

The composition of the bases also varies in 3′- and 5′-NTO. Thus, the content of G + C is higher in 5′-NTO than in 3′-NTO. This difference is especially noticeable in mRNA of warm-blooded vertebrates, in which the G + C content in 5′-NTO is 60%, and in 3′-NTO - 45% [9] .

Introns

There are introns inside the DNA regions corresponding to the 5′-UTR of the transcript, as well as in the DNA regions corresponding to the coding region of the mRNA. About 30% of the Metazoa genes have sites corresponding to 5′-NTO, consisting only of exons [4] . In humans, about 35% of genes have introns in 5′-NTO. Introns in 5′-UTR differ from those in the coding region and in 3′-UTR in nucleotide composition, length, and density [10] . It is known that the ratio of the total length of introns to the length of exons in 5′-NTO is less than in the coding region, however, the density of introns in 5′-NTO is higher (according to other data, on the contrary, lower [11] ), while introns are 5 ′ - NTO is approximately twice as long as the introns in the coding region. In 3′-NTO, introns are found much less frequently than in 5′-NTO [12] .

The evolution and functions of introns in 5′-NTOs remain largely unexplored. Nevertheless, it was found that actively expressed genes most often have short introns in 5′-NTO, than long ones or they are completely absent. Although the relationship between the length and number of introns and tissue has not yet been established, some correlation has been found between the number of introns in genes and their functions. So, especially many introns were identified in genes that perform regulatory functions [10] . In general, the presence of at least one intron in a 5′-NTO enhances gene expression, enhancing transcription (in this case we are talking about a DNA site corresponding to a 5′-NTO transcript) or stabilizing mature mRNA. For example, the expression of the ubiquitin C gene ( UbC ) depends on the presence of an intron in 5′-NTO. With the loss of the intron, the promoter activity drops sharply, and further studies have shown that transcription factors Sp1 and Sp3 bind in the 5′-UTR region of DNA [11] .

Secondary Structure

The structural and nucleotide composition of 5′-NTO is important for the regulation of gene expression; moreover, differences in the structure of 5′-NTO mRNA of the “household” genes and the genes involved in the regulation of ontogenesis were shown. 5′-UTR of genes, the expression of which is accompanied by the formation of a large amount of protein , as a rule, has a short length, they are characterized by a low content of G + C , the absence of pronounced elements of the secondary structure and internal AUG codons ( start codons ) located before the main start codon . On the contrary, 5′-UTR of genes giving rise to a small amount of protein have a longer length, higher GC content and have a large number of characteristic elements of the secondary structure. Highly structured 5′-NTOs are often inherent in the mRNA of genes involved in the regulation of development; Moreover, these formation of these mRNAs is often characterized by tissue and age specificity [13] .

It has been established that in 5′-NTOs, which have an overwhelming effect on translation, there are compact structures around the start codon . Although the specific mechanisms of such repression are unknown, it is believed that the nucleotide and structural features of 5′-NTO determine the binding of various protein factors that activate or suppress translation [13] .

 
The effect of G-quadruplexes in 5′-NTO on translation

Important and well-studied elements of the secondary structure of 5′-UTR are G-quadruplexes . They are formed when the sequences enriched in guanine are folded into an extremely stable non-canonical structure of four chains; such structures have a strictly suppressive effect on translation. Bioinformatics analysis revealed that G-quadruplexes are often highly conserved and are present in approximately 3000 human mRNAs [14] . Examples of such human mRNAs are estrogen receptor mRNA [15] , extracellular [16] , NRAS protooncogen [14] . In addition to 5′-NTO, G-quadruplexes were found in promoters , telomeres, and 3′-NTO. Especially a lot of G-quadruplexes in protein mRNA are involved in the regulation of translation and ontogenesis. The overwhelming effect of G-quadruplexes on the translation of the mRNA on which they are located may be due to both their secondary structure per se and their interaction with proteins and other factors [17] .

The scanning translation initiation model assumes that the small ribosome subunit moves along the mRNA (“scans”) in the direction from the 5′- to 3′-end in search of a suitable AUG start codon and starts broadcasting from it. It was also believed that the presence of stable elements of the secondary structure (for example, hairpins ) in 5′-NTO has an overwhelming effect on translation, since the ribosome is unable to pass through them. However, recent studies have shown that this is far from always the case. Translation of mRNA with a long, highly structured 5′-NTO can go no worse than mRNA with a short and unstructured 5′-NTO. This is explained by the fact that the suppressive effect of the secondary structure itself is often not expressed, since it is determined primarily by the proteins interacting with it. The prevailing erroneous point of view described above appeared due to the fact that earlier researchers used the rabbit reticulocyte lysate system ( rabbit reticulocyte lysate (RRL )), and this system had a number of drawbacks and did not meet the in vivo conditions [18] .

Alternative 5′-NTO

There are several mechanisms for the formation of alternative 5′-NTOs with the same coding sequence:

  • use of alternative promoters;
  • the formation of various 5′-NTOs during alternative splicing ;
  • the use of alternative sites of transcription initiation within the same promoter [19] .

The presence of different 5′-NTOs in the mRNA of the same gene provides additional opportunities for the regulation of its expression, since even small differences in the secondary structure of 5′-NTO can fundamentally affect the regulation of translation. Analysis of mammalian transcriptomes showed that the expression of alternative 5′-NTOs is a common phenomenon and a potentially large part of the genes can use this regulation mechanism. Protein products of genes that constantly use alternative 5′-NTOs are usually involved in processes such as transcription and signaling pathways . For example, the estrogen receptor β (ERβ) gene has 3 mRNAs with alternative 5′-NTOs giving rise to isoforms of the same protein, and often their activity is malfunctioned in cancer [19] .

Functions

Important functional elements that are involved in translation initiation and control of gene expression are localized inside 5′-NTO. This is evidenced, firstly, by the fact that the translation rate does not depend on the length and structure of 5′-NTO in both capped and uncaped mRNAs, as well as the fact that some genes are able to be expressed under stress [20] . The most important of these functional elements include sections of the internal ribosome landing ( IRES ), internal open reading frames of uORFs , iron-dependent element ( IRE ), etc.

IRES

 
Hepatitis C virus IRES element structure

The internal ribosome entry site (IRES ) is a regulatory mRNA motif that implements a cap-independent translation initiation mechanism in which ribosome landing occurs within the 5′-UTR, but near the site of the start of translation. The IRES mechanism is used by both capped and uncapped mRNAs under conditions when the cap-dependent translation initiation is suppressed due to stress , at a certain stage of the cell cycle and during apoptosis , providing continuous expression of the necessary proteins. A number of genes using IRES, for example, c-Myc , APAF1 , Bcl-2 genes , are expressed little under normal conditions and are activated due to IRES under stress. It is assumed that IRES can also take part in maintaining, under normal conditions, the low level of expression of a number of proteins, taking on ribosomes and preventing them from starting translation from the main initiation site. The mechanism of internal translation initiation is still poorly understood, although it is well known that the effectiveness of IRES is largely influenced by trans '' regulatory protein factors, which makes it possible for cell-specific use of IRES in translation [20] .

The structure of eukaryotic IRES is very different, and so far no conservative motifs characteristic of them have been established. For some genes, IRES requires specific stable elements of the secondary structure of mRNA; in other genes, on the contrary, they have an inhibitory effect on translation. It has been suggested that IRES are not static structures and undergo displacements, significantly changing their activity. IRES elements can also give rise to various protein isoforms , which provides additional opportunities for obtaining different protein products from the same gene [21] .

uORF

The internal open reading frames ( upstream open reading frames, uORF ) are located in the 5'-NTO and are characterized by the fact that their intra-frame stop codon is located after the internal start codon ( English upstream AUG, uAUG ), but before the main start codon , which is already in the broadcast (coding) region. uORFs were found in approximately 50% of 5'-UTR of human mRNAs , and their presence causes a decrease in gene expression, reducing the amount of functional mRNA by 30%, and protein formation by 30–80%. Ribosomes that bind to uAUG begin to translate uORF, which may adversely affect the translation efficiency of the main reading frame (i.e., the coding region). If there is no effective binding of the ribosome to the start codon in the coding region (i.e., translation initiation), the result is reduced protein formation, and hence the expression level of the corresponding gene. The opposite situation may occur: uORF translation will continue to translate the coding region, and as a result, too long a protein is formed, which can be harmful to the body. The decrease in translation efficiency due to the presence of uORF in 5'-NTO is a well-studied effect; one example illustrating it is the gene ( eng. poly (A) -polymerase α, PAPOLA ), whose mRNA contains two highly conserved uORFs in 5'-NTO. Mutation of proximal uAUG causes an increase in the translation efficiency of this mRNA, which indicates that uORF significantly reduces the expression of this gene . Another example is a thyroid hormone receptor that has an activating or repressing effect on the transcription of a number of target genes; strong repression of its translation is carried out by uORF with a length of 15 nucleotides inside the 5'-UTR of its mRNA [22] .

It is widely believed that uORFs reduce translation efficiency, because after termination of translation uORF the ribosome cannot restart translation and translate the coding region ( coding sequence, CDS ). However, recent studies of more than 500 loci of genes containing 5'-UTR have shown that there is no definite relationship between the effect of uORF on downstream gene expression and the distance between uORF and the coding sequence. Moreover, the authors of the study suggest that in genes containing a single uORF, it is most likely that CDS is translated after scanning the uORF with a ribosome without its dissociation, and not through translation reinitiation. This assumption is very different from the conclusions of Kozak (1987) and, in general, all ideas about uORF. Moreover, experiments with cells lacking Rent1 (a factor involved in the targeted destruction of defective mRNAs - English nonsense-mediated decay, NMD ) showed that in the absence of NMD, transcripts containing uORF were successfully translated. This shows that NMD also plays an important role in regulating the functioning of these transcripts. Most likely, there are several options for the development of events after the interaction of uORF and the ribosome: the continuation of translation, the continuation of scanning or the initiation of translation of the coding region, moreover, which one will occur depends on a number of factors [22] .

It was established that, in addition to AUG, codons that differ from AUG by one nucleotide can also be used as a translation start site, and the initiation efficiency in each case will be determined by the environment of the non-standard start codon [23] .

Although most uORF negatively affects gene expression, there are cases where the presence of uORF enhances translation. An example is the bi- cistronic mRNA of vpu-env HIV- 1 virus containing a conservative very small uORF. This uORF is located only 5 nucleotides before AUG vpu and soon ends with a stop codon overlapping with AUG vpu. It was found that this uORF has a significant positive effect on env translation and does not interfere with vpu translation. Mutants were obtained in which the distance between uORF and main AUG was increased by 5 nucleotides, and it was shown that uORF was not involved in vpu initiation. Based on this, the authors of the study suggested that this small uORF can serve as a ribosome retention site, during which the ribosome interacts with RNA structures that promote its advancement, that is, physically overcomes part of the 5'-UTR to reach the main initiator codon [24 ] .

In addition to the above, the following mechanisms of action of uORF are also known:

  • nucleotides located in uORF can form a hairpin that interferes with the progression of the ribosome;
  • not only cis , but also trans-regulation of translation of the coding region;
  • interaction with IRES [25] .

The significance of uORFs as regulatory elements involved in the regulation of ribosome binding and translation is well understood, but the function and even the fate of encoded uORF peptides is often unknown, possibly due to difficulties in analyzing the level of expression and localization of peptides [26] .

IRE

 
IRE mechanism of action

In 5′-NTO mRNA of proteins associated with iron metabolism, there is often a special regulatory element - an iron - dependent element . It is found in 5′-NTO mRNAs of proteins such as ferritin , , erythroid , mitochondrial aconitase , , metal transporter 1 (DMT1) ) [27] (however, it is also found in mRNAs of proteins that are not related to iron metabolism, for example, in mRNAs of the protein product of the CDC42BPA gene, a kinase involved in the reorganization of the cytoskeleton [28] ). IRE is a hairpin that interacts with - IRP1 and IRP2 ( English iron-regulatory proteins ). Когда концентрация железа мала, с IRE связываются IRP1 и IRP2, создавая преграды для рибосомы и делая трансляцию мРНК-мишени невозможной [29] . При высокой концентрации железа между этими белками и шпилькой нет жёсткого связывания, и идёт трансляция белков, задействованных в метаболизме железа. Кроме того, установлено, что трансляция белка- предшественника бета-амилоида также контролируется IRE, причём его IRE тоже способен связываться с IRP1 и IRP2, поэтому не исключено, что IRE может играть определённую роль в развитии болезни Альцгеймера [30] .

Другие взаимодействия с белками

В начала трансляции у эукариот на 5′-конце транскрипта в области кэпа собирается белковый комплекс , причём две его субъединицы — и — присоединяются в области 5′-НТО, ограничивая тем самым скорость, с которой может происходить инициация трансляции [31] . Однако роль 5′-НТО в образовании преинициаторного комплекса этим не ограничивается. В некоторых случаях с 5′-НТО связываются белки, препятствующие сборке инициаторного комплекса. В качестве примера можно рассмотреть регуляцию гена msl-2 ( англ. male-specific lethal 2 — мужская специфическая леталь 2), участвующего в определении пола у дрозофилы . С интроном, локализованным в 5′-НТО первичного транскрипта msl-2 , связывается белковый продукт гена SXL ( англ. sex lethal — половая леталь), в результате чего этот интрон не удаляется в ходе сплайсинга [29] . Он способствует одновременному связыванию с 5′-НТО и 3′-НТО белков , не позволяющих собраться инициаторному комплексу. Впрочем, SXL может подавлять трансляцию мРНК, лишённых поли(А)-хвоста или вообще 3′-НТО [32] . В мРНК , участвующей в метаболизме , и мРНК c-myc в 5′-НТО имеются шпилечные структуры, стабилизируемые белком-репрессором, препятствующие посадке на них рибосомы и сборке инициаторного комплекса. Варьирования в количестве белков-репрессоров обусловливают различную степень стабилизации этих шпилек и, соответственно, доступность этих 5′-НТО для инициаторных белков и рибосомы может быть различной [33] .

С 5′-НТО некоторых может связываться не только белок-репрессор, препятствующей сборке инициаторного комплекса и посадке рибосомы, но и белки-репрессоры, стабилизирующие различные структурные барьеры на пути сканирующего рибосомного комплекса. Например, трансляционная репрессия мРНК человека осуществляется продуктом её трансляции — тимидилатсинтазы — по принципу отрицательной обратной связи; тимидилатсинтаза взаимодействует с 30-нуклеотидной шпилькой в 5′-НТО, стабилизируя её и препятствуя продвижению рибосомы [34] .

Взаимодействие 5′-НТО и 3′-НТО

 
Circularization (ring closure) of mRNA

It is known that mRNA is capable of being locked into a ring (circularization) due to the interaction of special proteins that bind to the poly (A) tail , which facilitate the binding of factor eIF4F to the cap . As a result, mRNA takes on a closed form, translation initiation is stimulated, and translation efficiency is increased. However, in some cases, 5′-UTR and 3′-UTR of the same mRNA can bind to each other. So, the mRNA of the human p53 gene has regions in 5′-NTO and 3′-NTO, complementary to each other. By binding to each other and to the translation factor , they thereby contribute to an increase in the translation efficiency of p53 protein in response to DNA damage [35] .

Analysis of mRNAs of various human genes showed that 5′-UTR contains a motif that specifically interacts with the 3′-ends of miRNAs, and many of these miRNAs have a site at the 5′-end that is complementary to 3′-UTR. Further studies showed that the binding of 5′-NTO and 3′-NTO to the same miRNA facilitates the binding of the 5′-end of mRNA to the 3′-end, like a bridge, and mRNAs whose activity is significantly determined by miRNAs have predictable binding sites on both NTOs. Such mRNAs are called miBridge. It was further established that the loss of these binding sites reduced the repression of transcript translation driven by miRNAs. Thus, it was found that NTO binding sites with each other are necessary for suppressing mRNA translation. This suggests that the complementary interaction of 5′-NTO and 3′-NTO is necessary for the precise regulation of gene expression [36] .

5′-NTO prokaryotes and viruses

Bacteria

  External Images
 The structure diagram of a typical bacterial mRNA
 
3D structure of the [37]

The bacterial mRNA also contains 5′- and 3′-untranslated regions [38] [39] . The length of 5′-NTO of bacteria is much shorter than that of eukaryotes and usually amounts to 3-10 nucleotides. For example, the length of the 5′-UTR of the transcript of the lactose operon Escherichia coli is only 7 nucleotides [40] . The Shine – Dalgarno sequence ( AGGAGG ) [41] is localized in the 5′-NTO of bacteria [41] , which serves to bind the ribosome and is separated by a spacer from the AUG start codon . Although the 5′-NTOs of bacteria and eukaryotes are different, the addition of SS nucleotides to the spacer mRNA of the Ner gene of bacteriophage Mu , which is well expressed in Escherichia coli and Streptomyces cells, was successful in expressing this gene in rabbit reticulocyte cells [42] .

Elements of the secondary structure localized in 5′-NTO, as a rule, have an overwhelming effect on translation [43] . In particular, it is in 5′-NTO that are usually located — elements of operons that cause premature translation termination [44] (the most famous example of attenuation is the operation of the tryptophan operon ).

In addition, the majority of riboswitches [45], which are regulatory elements of mRNA that can bind to small molecules , are located in 5′-UTR of bacteria [45 ] .

Archaea

Untranslated regions are also found in the mRNA of many archaea . In particular, in the 5′- and 3′-NTO mRNA of the methanogenic archaea (as in other representatives of the Methanopyrales and Methanococcales orders), the SECIS element is responsible for the insertion of the amino acid selenocysteine into the polypeptide chain [47] .

It was found that the mRNAs of most haloarchae , as well as and lack pronounced 5′-UTR, but mRNAs of archaehemetanogens have long 5′-UTR. In this regard, it is assumed that the mechanism of translation initiation of methanogenic archaea can be different from that of other representatives of this domain [43] [48] .

In the 5′-NTO of the archaea, there is a that binds to thiamine pyrophosphate (TPP) (bacteria and eukaryotes also have such riboswitches) [49] .

Viruses

 
RNA is the poliovirus genome . In 5′-NTO is the IRES .

In many viruses , translation initiation occurs by a cap- independent mechanism and is carried out via the already mentioned IRES elements localized in 5′-UTR [50] . For example, this happens in HIV , hepatitis A and C viruses [51] . Such a translation initiation mechanism is convenient because in its case there is no need to scan a long fragment of 5′-NTO [40] .

Clinical Importance

Mutations affecting 5′-NTO often lead to the appearance of various diseases, since they disrupt the fine system of regulation of certain genes. The scheme below contains information about mutations affecting various regulatory elements of 5′-NTO and developing diseases in this case [1] (it should be clarified that hereditary hyperferritinemia / cataract syndrome develops with a mutation in IRE [1] [52] ).

 
Diseases that develop with various mutations in 5′-NTO

Notes

  1. ↑ 1 2 3 4 Sangeeta Chatterjee, Jayanta K. Pal. Role of 5- and 3-untranslated regions of mRNAs in human diseases // Biol. Cell. - 2009. - S. 251-262 . - DOI : 10.1042 / BC20080104 . (inaccessible link)
  2. ↑ Barrett et. al., 2013 , p. 9.
  3. ↑ Molecular biology glossary: ​​5 'Untranslated Region (5' UTR) (neopr.) .
  4. ↑ 1 2 Flavio Mignone, Carmela Gissi, Sabino Liuni, Graziano Pesole. Untranslated regions of mRNAs // Genome Biol .. - 2002. - T. 3 , No. 3 .
  5. ↑ Lodish, Havery. Molecular Cell Biology. - New York, New York: WH Freeman and Company, 2004 .-- P. 113. - ISBN 0-7167-4366-3 .
  6. ↑ Rhind, Nicholas; Chen, Zehua; Yassour, Moran; Thompson, Dawn A .; Haas, Brian J .; Habib, Naomi; Wapinski, Ilan; Roy, Sushmita; Lin, Michael F .; Heiman, David I .; Young, Sarah K .; Furuya, Kanji; Guo, Yabin; Pidoux, Alison; Chen, Huei Mei; Robbertse, Barbara; Goldberg, Jonathan M .; Aoki, Keita; Bayne, Elizabeth H .; Berlin, Aaron M .; Desjardins, Christopher A .; Dobbs, Edward; Dukaj, Livio; Fan, Lin; Fitzgerald, Michael G .; French, Courtney; Gujja, Sharvari; Hansen, Klavs; Keifenheim, Dan; Levin, Joshua Z. Comparative Functional Genomics of the Fission Yeasts (Eng.) // Science: journal. - 2011 .-- Vol. 332 , no. 6032 . - P. 930-936 . - DOI : 10.1126 / science.1203357 . - PMID 21511999 .
  7. ↑ Hereinafter, in the sections “Structure” and “Functions”, information on eukaryotic cellular 5′-UTR is provided. Data on 5′-UTR of bacteria, archaea, and viruses are discussed in the corresponding section.
  8. ↑ Mignone, Flavio; Graziano Pesole. mRNA Untranslated Regions (UTRs) ( unspecified ) . - 2011 .-- August 15. - DOI : 10.1002 / 9780470015902.a0005009.pub2 .
  9. ↑ Pesole G, Liuni S, Grillo G, Saccone C. Structural and compositional features of untranslated regions of eukaryotic mRNAs. (Eng.) // Gene . - Elsevier , 1997 .-- Vol. 205 , no. 1-2 . - P. 95-102 .
  10. ↑ 1 2 Cenik C., Derti A., Mellor JC, Berriz GF, Roth FP Genome-wide functional analysis of human 5 'untranslated region introns. . - 2010. - T. 11 , No. 3 . - DOI : 10.1186 / gb-2010-11-3-3-r29 .
  11. ↑ 1 2 Barrett et. al., 2013 , p. 21.
  12. ↑ Xin Hong, Douglas G. Scofield, Michael Lynch. Intron Size, Abundance, and Distribution within Untranslated Regions of Genes // Molecular Biology and Evolution . - Oxford University Press , 2006. - T. 23 , No. 12 . - S. 2392-2404 . - DOI : 10.1093 / molbev / msl11 .
  13. ↑ 1 2 Barrett et. al., 2013 , p. ten.
  14. ↑ 1 2 Kumari S. , Bugaut A. , Huppert JL , Balasubramanian S. An RNA G-quadruplex in the 5 'UTR of the NRAS proto-oncogene modulates translation. (English) // Nature chemical biology. - 2007. - Vol. 3, no. 4 . - P. 218-221. - DOI : 10.1038 / nchembio864 . - PMID 17322877 .
  15. ↑ Balkwill GD , Derecka K. , Garner TP , Hodgman C. , Flint AP , Searle MS Repression of translation of human estrogen receptor alpha by G-quadruplex formation. (English) // Biochemistry. - 2009. - Vol. 48, no. 48 . - P. 11487-11495. - DOI : 10.1021 / bi901420k . - PMID 19860473 .
  16. ↑ Morris MJ , Basu S. An unusually stable G-quadruplex within the 5'-UTR of the MT3 matrix metalloproteinase mRNA represses translation in eukaryotic cells. (English) // Biochemistry. - 2009. - Vol. 48, no. 23 . - P. 5313-5319. - DOI : 10.1021 / bi900498z . - PMID 19397366 .
  17. ↑ Barrett et. al., 2013 , p. eleven.
  18. ↑ Barrett et. al., 2013 , p. 12.
  19. ↑ 1 2 Barrett et. al., 2013 , p. 13.
  20. ↑ 1 2 Barrett et. al., 2013 , p. 14.
  21. ↑ Barrett et. al., 2013 , p. 15.
  22. ↑ 1 2 Barrett et. al., 2013 , p. sixteen.
  23. ↑ Barrett et. al., 2013 , p. 17.
  24. ↑ Barrett et. al., 2013 , p. 17-18.
  25. ↑ Somers, Joanna; Pöyry, Tuija; Willis, Anne E. A perspective on mammalian upstream open reading frame function (The English) // The International Journal of Biochemistry & Cell Biology : journal. - 2013 .-- Vol. 45 , no. 8 . - P. 1690-1700 . - DOI : 10.1016 / j.biocel.2013.04.0.020 . - PMID 23624144 .
  26. ↑ Barrett et. al., 2013 , p. 18.
  27. ↑ Paul Piccinelli, Tore Samuelsson. Evolution of the iron-responsive element // RNA. - 2007. - T. 13 , No. 7 . - S. 952-966 . - DOI : 10.1261 / rna.464807 .
  28. ↑ T. Leung, XQ Chen, I. Tan, E. Manser & L. Lim. Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization (Eng.) // Molecular and cellular biology : journal. - 1998 .-- January ( vol. 18 , no. 1 ). - P. 130-140 . - PMID 9418861 .
  29. ↑ 1 2 Araujo, Patricia R .; Yoon, Kihoon; Ko, Daijin; Smith, Andrew D .; Qiao, Mei; Suresh, Uthra; Burns, Suzanne C .; Penalva, Luiz OF Before It Gets Started: Regulating Translation at the 5 ′ UTR // Comparative and Functional Genomics: journal. - 2012. - Vol. 2012 . - P. 1 . - DOI : 10.1155 / 2012/475731 .
  30. ↑ Rogers, Jack T .; Bush, Ashley I .; Cho, Hyan-Hee; Smith, Deborah H .; Thomson, Andrew M .; Friedlich, Avi L .; Lahiri, Debomoy K .; Leedman, Peter J .; Huang, Xudong; Cahill, Catherine M. Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: Riboregulation against neural oxidative damage in Alzheimer's disease (Eng.) // Biochemical Society Transactions : journal. - 2008 .-- Vol. 36 , no. 6 . - P. 1282-1287 . - DOI : 10.1042 / BST0361282 . - PMID 19021541 .
  31. ↑ Kang, Min-Kook; Han, Seung-Jin. Post-transcriptional and post-translational regulation during mouse oocyte maturation (English) // BMB Reports: journal. - 2011 .-- Vol. 44 , no. 3 . - P. 147-157 . - DOI : 10.5483 / BMBRep.2011.44.3.147 . - PMID 21429291 .
  32. ↑ Penalva, LOF; Sanchez, L. RNA Binding Protein Sex-Lethal (Sxl) and Control of Drosophila Sex Determination and Dosage Compensation (Eng.) // Microbiology and Molecular Biology Reviews : journal. - American Society for Microbiology 2003. - Vol. 67 , no. 3 . - P. 343-359 . - DOI : 10.1128 / MMBR.67.3.343-359.2003 . - PMID 12966139 .
  33. ↑ Spirin, 2011 , p. 414-415.
  34. ↑ Spirin, 2011 , p. 416.
  35. ↑ Barrett et. al., 2013 , p. 32.
  36. ↑ Barrett et. al., 2013 , p. 32-33.
  37. ↑ Edwards TE, Ferré-D'Amaré AR Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition. (English) // Structure: journal. - 2006. - Vol. 14 , no. 9 . - P. 1459-1468 . - DOI : 10.1016 / j.str.2006.07.008 . - PMID 16962976 .
  38. ↑ Lewin B. Genes. - BINOM, 2012 .-- S. 144. - 896 p. - ISBN 978-5-94774-793-5 .
  39. ↑ N.V. Ravin, S.V. Shestakov. Prokaryotic genome // Vavilovsky Journal of Genetics and Breeding. - 2013. - T. 17 , No. 4/2 . - S. 972–984 .
  40. ↑ 1 2 Brown, TA Genomes 3. - New York, New York: Garland Science Publishing, 2007 .-- P. 397. - ISBN 0 8153 4138 5 .
  41. ↑ John W. Pelley. Elsevier's Integrated Review Biochemistry . - 2nd Edition. - 2012. - ISBN 978-0-32307-446-9 .
  42. ↑ A 5 ′ untranslated region which directs accurate and robust translation by prokaryotic and mammalian ribosomes .
  43. ↑ 1 2 Jian Zhang. Gene expression in Archaea: Studies of transcriptional promoters, messenger RNA processing, and five prime untranslated regions in Methanocaldococcus jannashchii . - 2009. Archived on May 31, 2014.
  44. ↑ Magali Naville, Daniel Gautheret. Transcription attenuation in bacteria: theme and variations // Brief Funct Genomic Proteomic. - 2009 .-- T. 8 . - S. 482-492 .
  45. ↑ Riboswitches: A Common RNA Regulatory Element (neopr.) .
  46. ↑ Nudler E., Mironov AS The riboswitch control of bacterial metabolism (Eng.) // Trends Biochem Sci : journal. - 2004. - Vol. 29 , no. 1 . - P. 11-7 . - DOI : 10.1016 / j.tibs.2003.11.004 . - PMID 14729327 .
  47. ↑ R. Wilting, S. Schorling, BC Persson, A. Bock. Selenoprotein Synthesis in Archaea: Identification of an mRNA Element of Methanococcus jannaschii Probably Directing Selenocysteine ​​Insertion // J. Mol. Biol .. - 1997.- T. 266 . - S. 637-641 .
  48. ↑ Brenneis M., Hering O., Lange C., Soppa J. Experimental characterization of Cis-acting elements important for translation and transcription in halophilic archaea. // PLoS Genet .. - 2007.- T. 3 , No. 12 . - DOI : 10.1371 / journal.pgen.0030229 .
  49. ↑ Kosuke Fujishima, Akio Kanai. Diversity, Function, and Processing of Archaeal Non-Coding RNAs // Sakura Y. Kato Archaea: Structure, Habitats and Ecological Significance. - Nova Science Publishers, Inc., 2011. - S. 69-94 . - ISBN 978-1-61761-932-8 . Archived on May 31, 2014.
  50. ↑ Thompson, Sunnie R. Tricks an IRES uses to enslave ribosomes (Eng.) // Trends in Microbiology : journal. - Cell Press 2012. - Vol. 20 , no. 11 . - P. 558-566 . - DOI : 10.1016 / j.tim.2012.08.08.002 . - PMID 22944245 .
  51. ↑ Jeffrey S. Kieft. Viral IRES RNA structures and ribosome interactions (English) // Trends in Biochemical Sciences. - Cell Press 2008. - Vol. 33 , no. 6 . - P. 274-283 . - DOI : 10.1016 / j.tibs.2008.04.007 .
  52. ↑ Barrett et. al., 2013 , p. nineteen.

Literature

  • Spirin A.S. Molecular Biology. Ribosomes and protein biosynthesis. - M .: Publishing Center "Academy", 2011. - 496 p. - ISBN 978-5-7695-6668-4 .
  • Konichev A.S., Sevastyanova G.A. Molecular biology. - Publishing Center "Academy", 2012. - 400 p. - ISBN 978-5-7695-9147-1 .
  • Lucy W. Barrett, Sue Fletcher, Steve D. Wilton. Untranslated Gene Regions and Other Non-coding Elements . - Springer Briefs in Biochemistry and Molecular Biology, 2013 .-- 57 p. - ISBN 978-3-0348-0679-4 .
Source - https://ru.wikipedia.org/w/index.php?title=5′- Non - broadcast region &oldid = 101001097


More articles:

  • Control freak
  • Leshru
  • Matalas Village Council
  • Manganese Lactate
  • J-Air
  • Dwarf, Leonid Borisovich
  • Battle of Bladensberg
  • Yamaguchi, Hotaru
  • Subash (river flows into Sivash)
  • Shiversky Village Council

All articles

Clever Geek | 2019