Journal
MOLECULAR CELL
Volume 81, Issue 16, Pages 3422-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2021.07.002
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Funding
- Institute for Basic Science from the Ministry of Science and ICT of Korea [IBS-R008-D1]
- BK21 Research Fellowship from the Ministry of Education of Korea
- NRF (National Research Foundation of Korea) - Korean government
- Ministry of Science & ICT (MSIT), Republic of Korea [IBS-R008-D1-2021-A00] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [4199990314450] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Only 758 pri-miRNAs are confidently processed by DROSHA, while the majority may be non-canonical or false entries. Analyses of the DROSHA-dependent pri-miRNAs show key cis-elements for processing, and widespread alternative processing and unproductive cleavage events were observed.
Maturation of canonical microRNA (miRNA) is initiated by DROSHA that cleaves the primary transcript (primiRNA). More than 1,800 miRNA loci are annotated in humans, but it remains largely unknown whether and at which sites pri-miRNAs are cleaved by DROSHA. Here, we performed in vitro processing on a full set of human pri-miRNAs (miRBase version 21) followed by sequencing. This comprehensive profiling enabled us to classify miRNAs on the basis of DROSHA dependence and map their cleavage sites with respective processing efficiency measures. Only 758 pri-miRNAs are confidently processed by DROSHA, while the majority may be non-canonical or false entries. Analyses of the DROSHA-dependent pri-miRNAs show key cis-elements for processing. We observe widespread alternative processing and unproductive cleavage events such as nick or inverse processing. SRSF3 is a broad-acting auxiliary factor modulating alternative processing and suppressing unproductive processing. The profiling data and methods developed in this study will allow systematic analyses of miRNA regulation.
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