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 |