RRC ID 46685
著者 Van Wynsberghe PM, Kai ZS, Massirer KB, Burton VH, Yeo GW, Pasquinelli AE.
タイトル LIN-28 co-transcriptionally binds primary let-7 to regulate miRNA maturation in Caenorhabditis elegans.
ジャーナル Nat Struct Mol Biol
Abstract The highly conserved let-7 microRNA (miRNA) regulates developmental pathways across animal phyla. Mis-expression of let-7 causes lethality in C. elegans and has been associated with several human diseases. We show that timing of let-7 expression in developing worms is under complex transcriptional and post-transcriptional control. Expression of let-7 primary transcripts oscillates during each larval stage, but precursor and mature let-7 miRNAs do not accumulate until later in development after LIN-28 protein has diminished. We demonstrate that LIN-28 binds endogenous primary let-7 transcripts co-transcriptionally. We further show that LIN-28 binds endogenous primary let-7 transcripts in the nuclear compartment of human ES cells, suggesting that this LIN-28 activity is conserved across species. We conclude that co-transcriptional interaction of LIN-28 with let-7 primary transcripts blocks Drosha processing and, thus, precocious expression of mature let-7 during early development.
巻・号 18(3)
ページ 302-8
公開日 2011-3-1
DOI 10.1038/nsmb.1986
PII nsmb.1986
PMID 21297634
PMC PMC3077891
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Line Gene Expression Regulation, Developmental* Humans MicroRNAs / genetics MicroRNAs / metabolism* Protein Binding Repressor Proteins / genetics Repressor Proteins / metabolism* Transcription, Genetic
IF 11.98
引用数 90
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm4344