Schematic of forms and functions of small RNA classes in nematodes, based on
C. elegans information. A) Mature microRNA (miRNA) strand,
derived from precursor miRNA, is incorporated into the miRNA-induced silencing
complex (miRISC) containing Argonaute protein (Ago). This complex directs
binding to mRNA target sequences, commonly in the 3’UTR. Binding
specificity is determined by complementarity between the target sequence and
miRNA seed sequence (nucleotides 2–7). B) Mature Piwi-interacting RNAs
(piRNA) (21U-RNA) are processed from a capped precursor and bind to Piwi
Argonaute PRG-1 to recognize target sequences, often transposons, by imperfect
complementary base-pairing. This initiates synthesis of secondary small
inhibitory RNAs (siRNAs) with 5’ triphosphate (5’TriP 22G-RNAs) by
RNA-dependent RNA polymerases (RdRPs) RRF-1 or EGO-1. 22G-RNAs associate with
worm-specific Argonaute proteins (WAGOs) to mediate target silencing. C)
Endogenous or exogenous double-stranded RNA (dsRNA) is processed by dicer into
siRNAs, which bind anti-sense to mRNA exonic sequence to mediate mRNA cleavage
by RDE-1 Argonaute. siRNAs also act as primers for synthesis of 22G-RNAs by
RRF-1 or EGO-1 to amplify the RNA interference (RNAi) response, using target
dsRNA as a template.