Abstract：
:The precise control of miR-17∼92 microRNA (miRNA) is essential for normal development, and overexpression of certain miRNAs from this cluster is oncogenic. Here, we find that the relative expression of the six miRNAs processed from the primary (pri-miR-17∼92) transcript is dynamically regulated during embryonic stem cell (ESC) differentiation. Pri-miR-17∼92 is processed to a biogenesis intermediate, termed "progenitor-miRNA" (pro-miRNA). Pro-miRNA is an efficient substrate for Microprocessor and is required to selectively license production of pre-miR-17, pre-miR-18a, pre-miR-19a, pre-miR-20a, and pre-miR-19b from this cluster. Two complementary cis-regulatory repression domains within pri-miR-17∼92 are required for the blockade of miRNA processing through the formation of an autoinhibitory RNA conformation. The endonuclease CPSF3 (CPSF73) and the spliceosome-associated ISY1 are responsible for pro-miRNA biogenesis and expression of all miRNAs within the cluster except miR-92. Thus, developmentally regulated pro-miRNA processing is a key step controlling miRNA expression and explains the posttranscriptional control of miR-17∼92 expression in development.
journal_name
Celljournal_title
Cellauthors
Du P,Wang L,Sliz P,Gregory RIdoi
10.1016/j.cell.2015.07.008subject
Has Abstractpub_date
2015-08-13 00:00:00pages
885-99issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(15)00845-4journal_volume
162pub_type
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