Small RNAs and silencing after transcription
In post-transcriptional silencing, small guide RNAs direct Argonaute complexes to target mRNAs. These complexes can promote cleavage, reduce translation or speed mRNA decay. Transcription can continue while protein output falls.
What a learner can do afterwards
- Explains how base pairing gives the silencing its specificity.
- Predicts mRNA changes under stated cleavage, decay or translation-only conditions, without treating abundance alone as proof of a mechanism.
- Predicts what a measurement of mRNA alone would miss in a silenced cell.
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This topic covers small RNAs acting on mRNA after transcription. A guide RNA in an Argonaute complex pairs with target RNA. Animal microRNAs often recognise sites in the 3 prime untranslated region using a short seed region. Other pairing and target context also affect silencing. One guide can regulate several messages. This pathway targets RNA, unlike promoter control of transcription.
Extensive pairing, including the central region, can allow an active slicing Argonaute to cleave mRNA. The fragments can decay. Pairing alone does not guarantee cleavage. Partial pairing can reduce translation and promote mRNA decay, so unchanged mRNA is not guaranteed. Lower abundance alone does not identify the decay mechanism.
mRNA abundance reflects production and loss. At steady state, these rates balance. If production stays fixed and decay becomes faster at each mRNA amount, the new balance has fewer messages. Thus confirmed cleavage that increases decay can lower steady-state mRNA abundance. This predicts the later balance, not which experimental readout must change first.
In a translation-only model, mRNA can stay unchanged while protein production falls. An mRNA-only assay misses that reduction. In real data, normal mRNA with low protein abundance does not prove a translation block: faster protein degradation is another possibility. mRNA abundance alone also does not measure transcription rate. Choose readouts that test the proposed mechanism.
Distinguish changing a guide from changing one target site. Removing a shared guide can relieve its repression of several messages. Altering only one message's recognition site can instead prevent recognition of that message while leaving the guide's other targets repressed. For this direct-effect prediction, hold the guide, other target sites and indirect regulation unchanged.
Pairing helps target recognition. Argonaute activity and context affect repression or decay. RNA abundance alone does not identify the mechanism.
Lesson, questions and flashcards written for this dataset.
Readings and flashcards written for this dataset. Non-coding RNA (ncRNA) is a Khan Academy video linked through YouTube.
More to read
Recognising RNA targets
A guide RNA directs an Argonaute complex towards RNA through complementary pairing. Animal microRNAs often recognise sites in the 3 prime untranslated region using a short seed region. Other pairing features and target context affect whether repression follows.
One guide can regulate several messages carrying suitable sites. A seed match is not a guarantee of silencing, and extensive pairing alone does not establish that Argonaute can slice.
Cleavage and decay
Suitable pairing can position a target for cleavage by an active slicing Argonaute. The resulting fragments can decay. If production remains fixed while decay becomes faster, steady-state message abundance decreases.
Direct slicing is not the only route to repression. Partial pairing can reduce translation and promote decay through other processes. Lower message abundance therefore needs additional evidence before it can be attributed to direct cleavage.
What expression measurements show
mRNA abundance reflects both production and loss. It does not directly report transcription or translation rates. Protein abundance also depends on both synthesis and degradation.
In a translation-only model, message abundance can remain unchanged while protein production falls. An mRNA-only assay misses that output change. In an experiment, normal mRNA with low protein is compatible with reduced translation but does not prove it. Further measurements must test the proposed cause.
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