Conditional
shRNA transcription using scDNAs. (a) Mechanism 5.
scDNA A detects mRNA detection target X (containing subsequence ‘a-b’)
and assembles with B to form a transcription template (containing
promoter, coding, and termination sequences), leading to transcription
of the shRNA Dicer substrate C targeting mRNA silencing target Y (containing
independent subsequence ‘z’). scDNAs A and B coexist
metastably in the absence of X. X assembles with A via toehold-mediated
3-way branch migration (step 1). Subsequently, X·A assembles
with B via toehold-mediated 4-way branch migration to produce a dsDNA
transcription template (step 2), mediating transcription of shRNA
Dicer substrate C with catalytic turnover. Domain lengths: |a| = 10,
|b| = 8, |p| = 8, |q| = 9, |t| = 7, |y| = 6, |z| = 19. (b) Conditional
transcription template formation. OFF state: minimal production of
transcription template A·B in the absence of short DNA detection
target Xs (‘a-b’), the presence of mRNA silencing
target Y, or the presence of mRNA off-target Z. ON state: strong production
of transcription template Xs·A·B in the presence
of Xs. (c) Conditional Dicer substrate transcription and
processing. OFF state: minimal transcription of Dicer substrate C
in the absence of short DNA detection target Xs (lane 1).
ON state: strong transcription of C in the presence of Xs (lane 3) and efficient Dicer processing of shRNA Dicer substrate
C (lane 4). (d) Quantification of the Dicer substrate band (C) in
lanes 1 and 3 of panel (c). See Section S6 for additional computational and experimental studies of Mechanism
5.