Mir384

RNAcentral ID: URS0000655E35_10090
Organism: Mus musculus
Review Status: COMPLETE
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Gene Description

Mir384 encodes the mouse mir-384 precursor. Its mature product, miR-384-5p, is a guide RNA that directs Argonaute/RISC to complementary sites in target mRNAs, the generic molecular role shared by all microRNAs. The best-supported specific role is in hippocampal synaptic plasticity: miR-384-5p is downregulated during long-term potentiation and is required for the maintenance phase of LTP and for dendritic spine enlargement, acting through repression of the kinase RSK3.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0035195 miRNA-mediated post-transcriptional gene silencing
IEA
GO_REF:0000115
ACCEPT
Summary: Rfam2GO annotation of the generic microRNA process; correct for a mir-384 precursor.
Reason: mir-384 is a bona fide microRNA precursor whose mature product guides RISC to target mRNAs. This is the gene's core biological process.
GO:1990830 cellular response to leukemia inhibitory factor
IEP
PMID:20439489
miRNA 34a, 100, and 137 modulate differentiation of mouse em...
MARK AS OVER ANNOTATED
Summary: Batch expression annotation from an embryonic-stem-cell differentiation screen in which mir-384 was never tested.
Reason: This row is one of 291 IEP annotations to the same term from a single paper. The experiment induced ESC differentiation by withdrawing LIF and recorded which miRNAs rose; only miR-34a, miR-100 and miR-137 were then functionally tested, and mir-384 is not discussed anywhere in the paper. A change in abundance after a cytokine is removed is also a poor match for "cellular response to leukemia inhibitory factor", which describes a cellular reaction to the presence of LIF. The expression observation may be real, but nothing here places mir-384 upstream of or within LIF signaling.
Supporting Evidence:
PMID:20439489
These results demonstrate that miR-34a, miR-100, and miR-137 are required for proper differentiation of mouse ESCs
PMID:20439489
The suppression of these three miRNAs by anti-miRs caused the block of ESC differentiation induced by LIF withdrawal
GO:0060291 long-term synaptic potentiation
IEP
PMID:25858512
miR-26a and miR-384-5p are required for LTP maintenance and ...
ACCEPT
Summary: Correct and central for mir-384, though the source paper supports it by functional perturbation rather than by expression alone.
Reason: miR-384-5p is one of the two miRNAs this paper demonstrates are required for LTP maintenance and spine enlargement, through repression of RSK3. The annotation is therefore right, and this row is the positive control for the 130-member IEP batch drawn from the same paper: the term is justified here precisely because the miRNA was functionally tested, which is not true of most of the cohort. The evidence code understates the support - the underlying experiments are electrophysiology and time-lapse spine imaging after miRNA manipulation, which is IMP rather than IEP.
Supporting Evidence:
PMID:25858512
we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3
PMID:25858512
the identification of miR-26a, miR-384-5p and let-7a as essential for LTP maintenance and enlargement of dendritic spines
GO:0003730 mRNA 3'-UTR binding
IDA
PMID:25858512
miR-26a and miR-384-5p are required for LTP maintenance and ...
NEW
Summary: Added so the core molecular function is represented in the annotation block. A 3' UTR reporter assay shows miR-384-5p acts through predicted binding sites in the RSK3 3' UTR.
Reason: GOA carries no molecular function for mir-384 beyond the generic Rfam process term. The source paper tested RSK3 as a direct target using mCherry reporters carrying the RSK3 3' UTR binding-site sequences, which supports mRNA 3'-UTR binding as the mature miRNA's molecular activity.
Supporting Evidence:
PMID:25858512
We generated miR-26a and miR-384-5p reporter constructs by inserting the sequences surrounding their predicted binding sites in the 3β€² UTR of RSK3 behind the destabilized mCherry gene

Core Functions

miRNA guide activity directing Argonaute/RISC to target mRNAs, deployed in hippocampal neurons to repress RSK3 and sustain long-term potentiation and dendritic spine enlargement

Supporting Evidence:
  • PMID:25858512
    we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3

References

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Suggested Questions for Experts

Q: Which additional mRNAs besides RSK3 does miR-384-5p repress in hippocampal neurons during LTP maintenance?

Suggested experts: synaptic plasticity researchers, microRNA biologists

Q: Is the requirement for miR-384-5p specific to the maintenance phase of LTP, or does it extend to other forms of long-lasting plasticity?

Suggested experts: electrophysiologists

Suggested Experiments

Experiment: Ago HITS-CLIP in hippocampal slices before and after LTP induction, comparing wild-type with miR-384 knockout

Hypothesis: miR-384-5p-dependent Argonaute occupancy changes at a defined target set during LTP maintenance

Type: high-throughput sequencing

Experiment: Conditional miR-384 deletion in CA1 followed by behavioural memory testing

Hypothesis: Loss of miR-384-5p impairs long-term memory consolidation, matching its requirement for LTP maintenance

Type: mouse genetics

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