miRNA targets and their functions

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miRNA Targets

The regulatory RNA molecules microRNA or miRNA binds to the mRNA through complementary base pairing irrespective of complete or incomplete binding. Recent studies have revealed that miRNAs specifically binds to the 3’UTRs of the target mRNA possessing either of the two binding patterns [1]. There are two classes of binding patterns [1] :

  1. One class of pattern consists of perfect Watson-Crick binding at the 5’-end of the miRNA. This region is known as “seed-region” and found at the 2-7 base of the miRNA. This region is able to suppress the target mRNAs without having a complete base pairing at the 3’-end of the miRNA.
  2. Another class involves the improper complementary base pairing at the 5’-end of the miRNAs, but to overcome this imperfect pairing, there are some additional base pairings at the 3’-end of the miRNA.

An mRNA can have multiple sites for a miRNA and also several miRNAs can bind to a single mRNA [2]. This kind of relation between mRNA and miRNA make the miRNA regulatory mechanism more complex [2].

miRNA Functions

Some studies have revealed that there are some miRNA intermediate duplexes which may have bulges within its one of the strands due to the inappropriate binding and mismatches [3]. These elements unwind the duplex and interfere in the silencing process [4]. There is some evidence indicating about controlling miRNA at the post-transcriptional level as the maturation of miRNA involves several steps which may be regulated [7,8,9]. It has been suggested from few studies that the expression of those miRNAs which originate from the introns of genes are transcribed along with the host genes [10-12,13], and is coupled with their host genes [14,15].

miRNAs in animals binds to the translational receptors partially to the 3’-UTR of the regulatory elements of the transcripts [16], without affecting the functions of the target sites and the 5’-UTR [17,18]. Another major silencing event of miRNAs destabilizes the target mRNAs and effect at the transcript level [19,20]. Some studies reveal that the miRNAs may have positive or negative regulatory effects [21]. Some evidence shows that under some conditions in some specific cell types, miRNAs can enhance translation [22].

miRNAs regulates the mRNAs and the RNAs and nothing seems to prevent this regulation [4]. It has been illustrated in a study done with Arabidopsis thaliana that miRNAs may bind to the pseudo targets in other non-coding RNAs to negatively regulate the miRNA activity [23].

There are many problems with the miRNA world which can be solved computationally, among which the miRNA target prediction is the essential one, as the function of miRNA depends on its target, therefore, in the cases of diseases such as cancer, it becomes necessary to predict the targets of miRNAs. We will discuss most common features of algorithms and tools for the miRNA target prediction in the upcoming articles.

 

References:

  1. Rajewsky N. microRNA target predictions in animals. Nat Genet 2006;38:S8–13.
  2. Bing Liu, Jiuyong Li, and Murray J. Cairns. Identifying miRNAs, targets and functions. Briefings in Bioinformatics. page 1-19; doi:10.1093/bib/bbs075.
  3. Khvorova,A., Reynolds,A. and Jayasena,S.D. (2003). Functional siRNAs and miRNAs exhibit strand bias. Cell, 115,209–216Khvorova,A., Reynolds,A. and Jayasena,S.D. (2003).Functional siRNAs and miRNAs exhibit strand bias. Cell, 115, 209–216.
  4. D. Mendes, A. T. Freitas and M.-F. Sagot. Current tools for the identification of miRNA genes and their targets. Nucleic Acids Research, 2009, Vol. 37, No. 8 2419–2433.doi:10.1093/nar/gkp145.
  5. Park,M.Y., Wu,G., Gonzalez-Sulser,A., Vaucheret,H. and Poethig,R.S. (2005) Nuclear processing and export of microRNAs in Arabidopsis. Proc. Natl Acad. Sci. USA, 102, 3691–3696.
  6. Bartel,D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism,and function. Cell, 116, 281–297.
  7. Cullen,B.R. (2004) Transcription and processing of human microRNA precursors. Mol. Cell, 16, 861–865.
  8. Ambros,V., Lee,R.C., Lavanway,A., Williams,P.T. and Jewell,D.(2003) MicroRNAs and other tiny endogenous RNAs in C. elegans.Biol., 13, 807–818.
  9. Luciano,D.J., Mirsky,H., Vendetti,N.J. and Maas,S. (2004) RNA editing of a miRNAprecursor. RNA, 10, 1174–1177.
  10. Lim,L.P., Lau,N.C., Weinstein,E.G., Abdelhakim,A., Yekta,S.,Rhoades,M.W., Burge,C.B. and Bartel,D.P. (2003) The microRNAs of Caenorhabditis elegans. Genes Dev., 17, 991–1008.
  11. Lai,E.C., Tomancak,P., Williams,R.W. and Rubin,G.M. (2003) Computational identification of Drosophila microRNA genes.Genome Biol., 4, R42.
  12. Rodriguez,A., Griffiths-Jones,S., Ashurst,J.L. and Bradley,A. (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res., 14, 1902–1910.
  13. Ying,S.-Y. and Lin,S.-L. (2005) Intronic microRNAs. Biochem.Res. Commun., 326, 515–520.
  14. Baskerville,S. and Bartel,D.P. (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA, 11, 241–247.
  15. Bartel,D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.
  16. Lai,E.C. (2002) Micro RNAs are complementary to 3’ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat. Genet., 30, 363–364.
  17. Kloosterman,W.P., Wienholds,E., Ketting,R.F. and Plasterk,R.H.A. (2004) Substrate requirements for let-7 function in the developing zebrafish embryo. Nucleic Acids Res., 32, 6284–6291.
  18. Lytle,J.R., Yario,T.A. and Steitz,J.A. (2007) Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5’ UTR as in the 3’ UTR. Proc. Natl Acad. Sci. USA, 104, 9667–9672.
  19. Lim,L.P., Lau,N.C., Garrett-Engele,P., Grimson,A., Schelter,J.M., Castle,J., Bartel,D.P., Linsley,P.S. and Johnson,J.M. (2005) Microarray analysis shows that some microRNAs downregulate
    large numbers of target mRNAs. Nature, 433, 769–773.
  20. Pillai,R.S. (2005) MicroRNA function: multiple mechanisms for a tiny RNA? RNA, 11, 1753–1761.
  21. Ambros,V. (2001) microRNAs: tiny regulators with great potential.Cell, 107, 823–826.
  22. Vasudevan,S., Tong,Y. and Steitz,J.A. (2007) Switching from repression to activation: microRNAs can up-regulate translation.Science, 318, 1931–1934.
  23. Chitwood,D.H., and Timmermans,M.C.P. (2007) Target mimics modulate miRNAs. Nat. Genet., 39, 935–936.
How to cite this article: Faiza, M., 2016. miRNA targets and their functions, 2(8):page 4-8. The article is available at http://bioinformaticsreview.com/20160802/mirna-targets-and-their-functions/
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Muniba is a Bioinformatician based in the South China University of Technology. She has cutting edge knowledge of bioinformatics tools, algorithms, and drug designing. When she is not reading she is found enjoying with the family. Know more about Muniba

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