期刊
CELL REPORTS
卷 26, 期 2, 页码 447-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.12.054
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资金
- National Cancer Institute
- federal funds from the Frederick National Laboratory for Cancer Research, NIH [HHSN261200800001E]
- NATIONAL CANCER INSTITUTE [ZIABC011566] Funding Source: NIH RePORTER
MicroRNA (miRNA) processing begins with Drosha cleavage, the fidelity of which is critical for downstream processing and mature miRNA target specificity. To understand how pri-miRNA sequence and structure influence Drosha cleavage, we studied the maturation of three pri-miR-9 paralogs, which encode the same mature miRNA but differ in the surrounding scaffold. We show that pri-miR-9-1 has a unique Drosha cleavage profile due to its distorted and flexible stem structure. Cleavage of pri-miR-9-1, but not pri-miR-9-2 or pri-miR-9-3, generates an alternative miR-9 with a shifted seed sequence that expands the scope of its target RNAs. Analyses of low-grade glioma patient samples indicate that the alternative-miR-9 has a potential role in tumor progression. Furthermore, we provide evidence that distortion of pri-miRNA stems induced by asymmetric internal loops correlates with Drosha cleavage at non-canonical sites. Our studies reveal that pri-miRNA paralogs can have distinct functions via differential Drosha processing.
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