Dynamic isomiR regulation in Drosophila development.
Several recent reports have demonstrated that microRNAs (miRNAs) can exhibit heterogeneous ends and post-transcriptional nontemplate 3' end additions of uridines or adenosines. Using two small RNA deep-sequencing data sets, we show here that these miRNA isoforms (isomiRs) are differentially expressed across Drosophila melanogaster development and tissues. Specifically, we demonstrate that: (1) nontemplate nucleotide additions of adenosines to miRNA 3' ends are highly abundant in early development; (2) a subset of miRNAs with nontemplate 3' Us are expressed in adult tissues; and (3) the size of at least eight "mature" (unmodified) miRNAs varies in a life-cycle or tissue-specific manner. These results suggest that subtle variability in isomiR expression, which is widely thought to be the result of inexact Dicer processing, is regulated and biologically meaningful. Indeed, a subset of the miRNAs enriched for 3' adenosine additions during early embryonic development, including miR-282 and miR-312, show enrichment for target sites in developmental genes that are expressed during late embryogenesis, suggesting that nontemplate additions increase miRNA stability or strengthen miRNA:target interactions. This work suggests that isomiR expression is an important aspect of miRNA biology, which warrants further investigation.
Fernandez-Valverde
Selene L
SL
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia.
Taft
Ryan J
RJ
Mattick
John S
JS
D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D030561:Databases, Nucleic Acid; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012689:Sequence Homology, Nucleic Acid
D035683:MicroRNAs
Genome Biol. 2007;8(7):R129
17615057
Genome Biol. 2009;10(3):R25
19261174
Genome Res. 2008 Apr;18(4):610-21
18285502
Dev Cell. 2003 Aug;5(2):337-50
12919683
Nucleic Acids Res. 2008 Jan;36(Database issue):D154-8
17991681
Development. 2008 Jun;135(11):1969-79
18434412
Genes Dev. 2010 Jan 15;24(2):129-34
20080951
Development. 2008 Apr;135(7):1201-14
18287206
Dev Biol. 2006 Jan 1;289(1):115-26
16325797
Genome Res. 2008 Oct;18(10):1571-81
18614752
Cell Commun Signal. 2009 Aug 10;7:18
19664273
Genome Biol. 2003;5(1):R1
14709173
Mol Cell. 2009 Nov 13;36(3):445-56
19917252
Development. 1998 May;125(10):1803-13
9550713
Nucleic Acids Res. 2009 May;37(8):2461-70
19255090
Nat Struct Mol Biol. 2010 Jan;17(1):24-30
20037596
Curr Biol. 2005 Aug 23;15(16):1501-7
16111943
Nat Struct Mol Biol. 2008 Sep;15(9):902-9
19172742
Genes Dev. 2009 Feb 15;23(4):433-8
19240131
Genome Res. 2009 Jul;19(7):1175-83
19336450
Mol Cell. 2009 Nov 13;36(3):431-44
19917251
Genome Res. 2010 Feb;20(2):257-64
20051556
Genetics. 2008 Jan;178(1):307-23
18202376
RNA. 2010 Jan;16(1):43-56
19917635
Nat Rev Genet. 2009 Feb;10(2):94-108
19148191
PLoS One. 2009;4(3):e4669
19252745
Curr Biol. 2008 Jun 3;18(11):795-802
18501606
Genetics. 2008 Apr;178(4):2017-29
18430932
Cell. 2004 Nov 24;119(5):641-51
15550246
Nat Methods. 2009 Jul;6(7):474-6
19564845
Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):7964-9
18524951
Genome Res. 2007 Dec;17(12):1850-64
17989254
Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15907-11
16249329
Genetics. 2000 Apr;154(4):1649-62
10747060
Nat Cell Biol. 2009 Sep;11(9):1157-63
19701194
Cell. 2007 Jun 29;129(7):1401-14
17604727
Cell. 2009 Jan 23;136(2):215-33
19167326
Curr Biol. 2008 Jan 22;18(2):147-51
18207740
Nat Rev Mol Cell Biol. 2009 Feb;10(2):141-8
19145236
Nucleic Acids Res. 2009 Apr;37(6):1878-85
19188256
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14644-9
18780789