期刊
NUCLEIC ACIDS RESEARCH
卷 48, 期 12, 页码 6874-6888出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa386
关键词
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资金
- European Research Council [RNAmedTGS]
- MSD Avenir [HideInflameSeq]
- Ministere de l'Enseignement Superieur et de la Recherche et de l'Innovation scholarship
- Japan Society for the Promotion of Science [17K15601, 19K16523, 16K08590, 19K07370]
- ERC, RNA MedTGS
- Grants-in-Aid for Scientific Research [19K07370, 19K16523, 17K15601, 16K08590] Funding Source: KAKEN
MicroRNAs (miRNAs) are predicted to regulate the expression of >60% of mammalian genes and play fundamental roles in most biological processes. Deregulation of miRNA expression is a hallmark of most cancers and further investigation of mechanisms controlling miRNA biogenesis is needed. The double stranded RNA-binding protein, NF90 has been shown to act as a competitor of Microprocessor for a limited number of primary miRNAs (pri-miRNAs). Here, we show that NF90 has a more widespread effect on pri-miRNA biogenesis than previously thought. Genome-wide approaches revealed that NF90 is associated with the stem region of 38 pri-miRNAs, in a manner that is largely exclusive of Microprocessor. Following loss of NF90, 22 NF90-bound pri-miRNAs showed increased abundance of mature miRNA products. NF90-targeted pri-miRNAs are highly stable, having a lower free energy and fewer mismatches compared to all pri-miRNAs. Mutations leading to less stable structures reduced NF90 binding while increasing pri-miRNA stability led to acquisition of NF90 association, as determined by RNA electrophoretic mobility shift assay (EMSA). NF90-bound and downregulated pri-miRNAs are embedded in introns of host genes and expression of several host genes is concomitantly reduced. These data suggest that NF90 controls the processing of a subset of highly stable, intronic miRNAs.
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