Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Export

@article{citeulike:2651699, abstract = {RNA interference (RNAi) is a mechanism by which double-stranded RNAs (dsRNAs) suppress specific transcripts in a sequence-dependent manner. dsRNAs are processed by Dicer to 21-24-nucleotide small interfering RNAs (siRNAs) and then incorporated into the argonaute (Ago) proteins. Gene regulation by endogenous siRNAs has been observed only in organisms possessing RNA-dependent RNA polymerase (RdRP). In mammals, where no RdRP activity has been found, biogenesis and function of endogenous siRNAs remain largely unknown. Here we show, using mouse oocytes, that endogenous siRNAs are derived from naturally occurring dsRNAs and have roles in the regulation of gene expression. By means of deep sequencing, we identify a large number of both approximately 25-27-nucleotide Piwi-interacting RNAs (piRNAs) and approximately 21-nucleotide siRNAs corresponding to messenger RNAs or retrotransposons in growing oocytes. piRNAs are bound to Mili and have a role in the regulation of retrotransposons. siRNAs are exclusively mapped to retrotransposons or other genomic regions that produce transcripts capable of forming dsRNA structures. Inverted repeat structures, bidirectional transcription and antisense transcripts from various loci are sources of the dsRNAs. Some precursor transcripts of siRNAs are derived from expressed pseudogenes, indicating that one role of pseudogenes is to adjust the level of the founding source mRNA through RNAi. Loss of Dicer or Ago2 results in decreased levels of siRNAs and increased levels of retrotransposon and protein-coding transcripts complementary to the siRNAs. Thus, the RNAi pathway regulates both protein-coding transcripts and retrotransposons in mouse oocytes. Our results reveal a role for endogenous siRNAs in mammalian oocytes and show that organisms lacking RdRP activity can produce functional endogenous siRNAs from naturally occurring dsRNAs.}, author = {Watanabe, Toshiaki and Totoki, Yasushi and Toyoda, Atsushi and Kaneda, Masahiro and Kuramochi-Miyagawa, Satomi and Obata, Yayoi and Chiba, Hatsune and Kohara, Yuji and Kono, Tomohiro and Nakano, Toru and Surani, M. Azim and Sakaki, Yoshiyuki and Sasaki, Hiroyuki}, citeulike-article-id = {2651699}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature06908}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature06908}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18404146}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18404146}, day = {22}, doi = {10.1038/nature06908}, issn = {1476-4687}, journal = {Nature}, keywords = {ago, ago2, argonaute, dicer, dsrna, germline, oocyte, rdrp, sirna}, month = {May}, number = {7194}, pages = {539--543}, posted-at = {2009-08-18 15:54:16}, priority = {5}, publisher = {Nature Publishing Group}, title = {Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes.}, url = {http://dx.doi.org/10.1038/nature06908}, volume = {453}, year = {2008} }

TY - JOUR ID - citeulike:2651699 L3 - citeulike-article-id:2651699 N2 - RNA interference (RNAi) is a mechanism by which double-stranded RNAs (dsRNAs) suppress specific transcripts in a sequence-dependent manner. dsRNAs are processed by Dicer to 21-24-nucleotide small interfering RNAs (siRNAs) and then incorporated into the argonaute (Ago) proteins. Gene regulation by endogenous siRNAs has been observed only in organisms possessing RNA-dependent RNA polymerase (RdRP). In mammals, where no RdRP activity has been found, biogenesis and function of endogenous siRNAs remain largely unknown. Here we show, using mouse oocytes, that endogenous siRNAs are derived from naturally occurring dsRNAs and have roles in the regulation of gene expression. By means of deep sequencing, we identify a large number of both approximately 25-27-nucleotide Piwi-interacting RNAs (piRNAs) and approximately 21-nucleotide siRNAs corresponding to messenger RNAs or retrotransposons in growing oocytes. piRNAs are bound to Mili and have a role in the regulation of retrotransposons. siRNAs are exclusively mapped to retrotransposons or other genomic regions that produce transcripts capable of forming dsRNA structures. Inverted repeat structures, bidirectional transcription and antisense transcripts from various loci are sources of the dsRNAs. Some precursor transcripts of siRNAs are derived from expressed pseudogenes, indicating that one role of pseudogenes is to adjust the level of the founding source mRNA through RNAi. Loss of Dicer or Ago2 results in decreased levels of siRNAs and increased levels of retrotransposon and protein-coding transcripts complementary to the siRNAs. Thus, the RNAi pathway regulates both protein-coding transcripts and retrotransposons in mouse oocytes. Our results reveal a role for endogenous siRNAs in mammalian oocytes and show that organisms lacking RdRP activity can produce functional endogenous siRNAs from naturally occurring dsRNAs. IS - 7194 JF - Nature SN - 1476-4687 EP - 543 TI - Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. PB - Nature Publishing Group VL - 453 SP - 539 KW - ago KW - ago2 KW - argonaute KW - dicer KW - dsrna KW - germline KW - oocyte KW - rdrp KW - sirna AU - Watanabe, Toshiaki AU - Totoki, Yasushi AU - Toyoda, Atsushi AU - Kaneda, Masahiro AU - Kuramochi-Miyagawa, Satomi AU - Obata, Yayoi AU - Chiba, Hatsune AU - Kohara, Yuji AU - Kono, Tomohiro AU - Nakano, Toru AU - Surani, Azim AU - Sakaki, Yoshiyuki AU - Sasaki, Hiroyuki PY - 2008/05/22/ UR - http://dx.doi.org/10.1038/nature06908 ER -