:IsomiR

miRBase is considered to be the gold-standard miRNA database—it stores miRNA sequences detected by thousand of experiments. In this database each miRNA is associated with a miRNA precursor and with one or two mature miRNA (-5p and -3p). In the past it had always been said that the same miRNA precursor generates the same miRNA sequences. However, the advent of deep sequencing has now allowed researchers to detect a huge variability in miRNA biogenesis, meaning that from the same miRNA precursor many different sequences can be generated potentially have different targets,{{Cite journal|last1=Llorens|first1=Franc|last2=Bañez-Coronel|first2=Mónica|last3=Pantano|first3=Lorena|last4=del Río|first4=Jose Antonio|last5=Ferrer|first5=Isidre|last6=Estivill|first6=Xavier|last7=Martí|first7=Eulàlia|date=2013-02-15|title=A highly expressed miR-101 isomiR is a functional silencing small RNA|journal=BMC Genomics|volume=14|pages=104|doi=10.1186/1471-2164-14-104|issn=1471-2164|pmc=3751341|pmid=23414127 |doi-access=free }}{{Cite journal|last1=Telonis|first1=Aristeidis G.|last2=Loher|first2=Phillipe|last3=Jing|first3=Yi|last4=Londin|first4=Eric|last5=Rigoutsos|first5=Isidore|date=2015-10-30|title=Beyond the one-locus-one-miRNA paradigm: microRNA isoforms enable deeper insights into breast cancer heterogeneity|journal=Nucleic Acids Research|volume=43|issue=19|pages=9158–9175|doi=10.1093/nar/gkv922|issn=1362-4962|pmc=4627084|pmid=26400174}}{{Cite journal|last1=Mercey|first1=Olivier|last2=Popa|first2=Alexandra|last3=Cavard|first3=Amélie|last4=Paquet|first4=Agnès|last5=Chevalier|first5=Benoît|last6=Pons|first6=Nicolas|last7=Magnone|first7=Virginie|last8=Zangari|first8=Joséphine|last9=Brest|first9=Patrick|last10=Zaragosi|first10=Laure-Emmanuelle|last11=Ponzio|first11=Gilles|last12=Lebrigand|first12=Kevin|last13=Barbry|first13=Pascal|last14=Marcet|first14=Brice|

date=2017-02-13|title=Characterizing isomiR variants within the microRNA-34/449 family|journal=FEBS Letters|doi=10.1002/1873-3468.12595|issn=1873-3468|pmid=28192603|volume=591|issue=5|pmc=5363356|pages=693–705}} or even lead to opposite changes in mRNA expression.

The advent of sequencing has permitted scientists to elucidate a huge landscape of new miRNAs, to increase our knowledge of the biogenesis involved and to discover putative post-transcriptional editing processes in miRNAs ignored until now. These processes mostly generate variations of the current miRNAs that are annotated in miRBase in the 3' and 5' terminus and in minor frequencies, nucleotide substitution along the miRNA length.{{Cite journal | last1 = Ebhardt | first1 = H. A. | last2 = Tsang | first2 = H. H. | last3 = Dai | first3 = D. C. | last4 = Liu | first4 = Y. | last5 = Bostan | first5 = B. | last6 = Fahlman | first6 = R. P. | title = Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications | journal = Nucleic Acids Research | volume = 37 | issue = 8 | pages = 2461–2470 | year = 2009 | pmid = 19255090 | pmc = 2677864 | doi = 10.1093/nar/gkp093}}{{Cite journal | last1 = Iida | first1 = K. | last2 = Jin | first2 = H. | last3 = Zhu | first3 = J. K. | title = Bioinformatics analysis suggests base modifications of tRNAs and miRNAs in Arabidopsis thaliana | journal = BMC Genomics | volume = 10 | pages = 155 | year = 2009 | pmid = 19358740 | pmc = 2674459 | doi = 10.1186/1471-2164-10-155 | doi-access = free }}{{Cite journal | last1 = Pantano | first1 = L. | last2 = Estivill | first2 = X. | last3 = Marti | first3 = E. | title = SeqBuster, a bioinformatic tool for the processing and analysis of small RNAs datasets, reveals ubiquitous miRNA modifications in human embryonic cells | journal = Nucleic Acids Research | volume = 38 | issue = 5 | pages = e34 | year = 2009 | pmid = 20008100 | pmc = 2836562 | doi = 10.1093/nar/gkp1127}}{{Cite journal | last1 = Marti | first1 = E. | last2 = Pantano | first2 = L. | last3 = Bañez-Coronel | first3 = M. | last4 = Llorens | first4 = F. | last5 = Miñones-Moyano | first5 = E. | last6 = Porta | first6 = S. | last7 = Sumoy | first7 = L. | last8 = Ferrer | first8 = I. | last9 = Estivill | first9 = X. | title = A myriad of miRNA variants in control and Huntington's disease brain regions detected by massively parallel sequencing | journal = Nucleic Acids Research | volume = 38 | issue = 20 | pages = 7219–7235 | year = 2010 | pmid = 20591823 | pmc = 2978354 | doi = 10.1093/nar/gkq575}} The variations are mainly generated by a shift of Drosha and Dicer in the cleavage site, but also by nucleotide additions at the 3'-end,{{Cite journal | last1 = Lu | first1 = S. | last2 = Sun | first2 = Y. -H. | last3 = Chiang | first3 = V. L. | title = Adenylation of plant miRNAs | journal = Nucleic Acids Research | volume = 37 | issue = 6 | pages = 1878–1885 | year = 2009 | pmid = 19188256 | pmc = 2665221 | doi = 10.1093/nar/gkp031}} resulting in new sequences different from the annotated miRNA. These were named "isomiRs" by Morin et al., 2008. IsomiRs have been well established along different species in metazoa{{Cite journal | last1 = Reid | first1 = J. G. | last2 = Nagaraja | first2 = A. K. | last3 = Lynn | first3 = F. C. | last4 = Drabek | first4 = R. B. | last5 = Muzny | first5 = D. M. | last6 = Shaw | first6 = C. A. | last7 = Weiss | first7 = M. K. | last8 = Naghavi | first8 = A. O. | last9 = Khan | first9 = M. | last10 = Zhu | first10 = H. | last11 = Tennakoon | first11 = J. | last12 = Gunaratne | first12 = G. H. | last13 = Corry | first13 = D. B. | last14 = Miller | first14 = J. | last15 = McManus | first15 = M. T. | last16 = German | first16 = M. S. | last17 = Gibbs | first17 = R. A. | last18 = Matzuk | first18 = M. M. | last19 = Gunaratne | first19 = P. H. | title = Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5′-seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes | journal = Genome Research | volume = 18 | issue = 10 | pages = 1571–1581 | year = 2008 | pmid = 18614752 | pmc = 2556275 | doi = 10.1101/gr.078246.108}}{{Cite journal | last1 = Luciano | first1 = D. J. | last2 = Mirsky | first2 = H. | last3 = Vendetti | first3 = N. J. | last4 = Maas | first4 = S. | title = RNA editing of a miRNA precursor | journal = RNA | volume = 10 | issue = 8 | pages = 1174–1177 | year = 2004 | pmid = 15272117 | pmc = 1370607 | doi = 10.1261/rna.7350304}}{{Cite journal | last1 = Guo | first1 = L. | last2 = Lu | first2 = Z. | title = Global expression analysis of miRNA gene cluster and family based on isomiRs from deep sequencing data | journal = Computational Biology and Chemistry | volume = 34 | issue = 3 | pages = 165–171 | year = 2010 | pmid = 20619743 | doi = 10.1016/j.compbiolchem.2010.06.001}}{{Cite journal | last1 = Brennecke | first1 = J. | last2 = Aravin | first2 = A. A. | last3 = Stark | first3 = A. | last4 = Dus | first4 = M. | last5 = Kellis | first5 = M. | last6 = Sachidanandam | first6 = R. | last7 = Hannon | first7 = G. J. | title = Discrete Small RNA-Generating Loci as Master Regulators of Transposon Activity in Drosophila | journal = Cell | volume = 128 | issue = 6 | pages = 1089–1103 | year = 2007 | pmid = 17346786 | doi = 10.1016/j.cell.2007.01.043| s2cid = 2246942 | url = https://authors.library.caltech.edu/95370/2/1-s2.0-S0092867407002577-mmc1.pdf | doi-access = free }}{{Cite journal | last1 = Bizuayehu | first1 = T. T. | last2 = Lanes | first2 = C. F. C. | last3 = Furmanek | first3 = T. | last4 = Karlsen | first4 = B. O. | last5 = Fernandes | first5 = J. M. O. | last6 = Johansen | first6 = S. D. | last7 = Babiak | first7 = I. | title = Differential expression patterns of conserved miRNAs and isomiRs during Atlantic halibut development | journal = BMC Genomics | volume = 13 | pages = 11 | year = 2012| doi = 10.1186/1471-2164-13-11 | pmid = 22233483 | pmc = 3398304 | doi-access = free }} and deeply described for the first time in human stem cells and human brain samples. Moreover, it has been proven that isomiRs are not caused by RNA degradation during sample preparation for next generation sequencing.{{Cite journal | last1 = Lee | first1 = L. W. | last2 = Zhang | first2 = S. | last3 = Etheridge | first3 = A. | last4 = Ma | first4 = L. | last5 = Martin | first5 = D. | last6 = Galas | first6 = D. | last7 = Wang | first7 = K. | title = Complexity of the microRNA repertoire revealed by next-generation sequencing | journal = RNA | volume = 16 | issue = 11 | pages = 2170–2180 | year = 2010 | pmid = 20876832 | pmc = 2957056 | doi = 10.1261/rna.2225110}} Some studies have tried to explain the miRNA diversity by structural bases of precursors but without clear results.{{Cite journal | last1 = Starega-Roslan | first1 = J. | last2 = Krol | first2 = J. | last3 = Koscianska | first3 = E. | last4 = Kozlowski | first4 = P. | last5 = Szlachcic | first5 = W. J. | last6 = Sobczak | first6 = K. | last7 = Krzyzosiak | first7 = W. J. | title = Structural basis of microRNA length variety | journal = Nucleic Acids Research | volume = 39 | issue = 1 | pages = 257–268 | year = 2010 | pmid = 20739353 | pmc = 3017592 | doi = 10.1093/nar/gkq727}} The functionality of adenylation or uridynilation at the 3'end (3'addition isomiRs) has been related to alterations in the miRNA-3'-UTR stability.{{Cite journal | last1 = Burroughs | first1 = A. M. | last2 = Ando | first2 = Y. | last3 = De Hoon | first3 = M. J. L. | last4 = Tomaru | first4 = Y. | last5 = Nishibu | first5 = T. | last6 = Ukekawa | first6 = R. | last7 = Funakoshi | first7 = T. | last8 = Kurokawa | first8 = T. | last9 = Suzuki | first9 = H. | last10 = Hayashizaki | first10 = Y. | last11 = Daub | first11 = C. O. | title = A comprehensive survey of 3′ animal miRNA modification events and a possible role for 3′ adenylation in modulating miRNA targeting effectiveness | journal = Genome Research | volume = 20 | issue = 10 | pages = 1398–1410 | year = 2010 | pmid = 20719920 | pmc = 2945189 | doi = 10.1101/gr.106054.110}} Furthermore, differential expression of isomiRs has been detected during development in D. melanogaster and Hippoglossus hippoglossus L., suggesting a biological function.{{Cite journal | last1 = Fernandez-Valverde | first1 = S. L. | last2 = Taft | first2 = R. J. | last3 = Mattick | first3 = J. S. | title = Dynamic isomiR regulation in Drosophila development | journal = RNA | volume = 16 | issue = 10 | pages = 1881–1888 | year = 2010 | pmid = 20805289 | pmc = 2941097 | doi = 10.1261/rna.2379610}}

• Trimming variants: these are possible due to slight variations by Drosha and/or Dicer
• Nucleotide addition: Wyman et al.{{Cite journal | last1 = Wyman | first1 = S. K. | last2 = Knouf | first2 = E. C. | last3 = Parkin | first3 = R. K. | last4 = Fritz | first4 = B. R. | last5 = Lin | first5 = D. W. | last6 = Dennis | first6 = L. M. | last7 = Krouse | first7 = M. A. | last8 = Webster | first8 = P. J. | last9 = Tewari | first9 = M. | title = Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity | journal = Genome Research | volume = 21 | issue = 9 | pages = 1450–1461 | year = 2011 | pmid = 21813625 | pmc = 3166830 | doi = 10.1101/gr.118059.110}} have described the process of nucleotide transferases adding individual nucleotides to miRNA sequences
• Nucleotide substitution: there is a huge range of possible changes in such an event, some of them can be explained by current Adenosine_deaminase like A to G or C to U, in a similar way to what happens in post-transcriptional RNA editing events involving mRNA.

{{reflist|30em}}

• [http://www.mirbase.org/ miRBase]

Category:MicroRNA

Category:RNA

Category:Gene expression