Dear Nina Raver-Shapira,
نویسندگان
چکیده
Drosha is a member of the ribonuclease (RNase) III family that selectively process RNAs with prominent double-stranded features. Drosha plays a key role in the generation of precursor microRNAs from primary microRNA (pri-miRNA) transcripts in animal cells, yet how Drosha recognizes its RNA substrates remains incompletely understood. Previous studies have indicated that, within the context of a larger pri-miRNA, an approximately 80nucleotide-long RNA hairpin structure is necessary for processing by Drosha. Here, by performing in vitro Drosha processing reactions with RNA substrates of various sizes and structures, we show that Drosha function also requires single-stranded RNA extensions located outside the primiRNA hairpin. The sequence of these RNA extensions was largely unimportant, but a strong secondary structure within the extension, or a blunt-ended primiRNA hairpin, blocked Drosha cleavage. The requirement for single-stranded extensions on the pri-miRNA hairpin substrate for Drosha processing is currently unique among the RNase III enzymes. Ribonuclease (RNase) 1 III family enzymes are expressed in both prokaryotes and eukaryotes and are involved in the processing, maturation, and degradation of a wide variety of RNAs, including ribosomal RNAs, transfer RNAs, small nuclear RNAs, small nucleolar RNAs, microRNAs (miRNAs), and small interfering RNAs (siRNAs) (1, 2). These RNases generate RNA products that feature an imperfect or perfect duplex with an ~2 nucleotide (nt) 3’ overhang at the site of cleavage. This characteristic staggered 3’ end structure results from the independent cleavage of the two RNA strands by the two catalytic sites located within a single double-stranded RNA (dsRNA) processing center formed by two RNase III domains. These RNase III domains may derive from two proteins, as seen with bacterial RNase III, or from a single protein, as seen with Dicer and Drosha (3, 4).
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