Fig. 6: Multiple mechanisms to ensure the accuracy of dicing.

a Coarse measurement of DICER by end-binding pockets. The initial interaction between 5p- and 3p-end binding pockets of DICER and the ends of RNA positions the DICER catalytic center approximately 21–22 nucleotides from the RNA ends. Consequently, DICER is predisposed to cleave RNA around the DC21 and DC22 sites. b Fine measurement of DICER is conducted by multiple mechanisms. Bulge model: Bulges on the 3p-strand positioned 22 and 23 nucleotides from the 5p-end of RNAs are known to enhance DICER cleavage at DC21 and DC22, respectively. mWCU model: An mWCU motif located 17 or 18 nucleotides from the 5p-end of RNAs enhances DICER cleavage at DC21 and DC22, respectively. This enhancement is attributed to interactions between the motif and residue R1855 within the dsRBD domain of DICER. Double YCR model: The incorporation of a double YCR motif at the 19 and 20 nucleotides from the 5p-end of RNAs prompts DICER to cleave at DC21 and DC22, respectively. This process involves the participation of residues E1564 and E1813. Bipartite pairing model: The two base pairs located immediately upstream of the cleavage sites, at positions −1 and −2, are integral for cleavage efficiency at DC21 or DC22. Consequently, a mismatch at the −1 position relative to the DC21 site can stimulate cleavage at DC22 by impeding cleavage at DC21, and vice versa.