Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.26.5 (
RNase P
)
1,348
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
N
6
-methyladenosine (m
6
A) is the most abundant internal modification in RNAs and plays regulatory roles in a variety of biological and physiological processes. Despite its important roles, the molecular mechanism underlying m
6
A-mediated gene regulation is poorly understood. Here, we show that m
6
A-containing RNAs are subject to endoribonucleolytic cleavage via
YTHDF2
(m
6
A reader protein), HRSP12 (adaptor protein), and
RNase P
/MRP (endoribonucleases). We demonstrate that HRSP12 functions as an adaptor to bridge
YTHDF2
and
RNase P
/MRP, eliciting rapid degradation of
YTHDF2
-bound RNAs. Transcriptome-wide analyses show that m
6
A RNAs that are preferentially targeted for endoribonucleolytic cleavage have an HRSP12-binding site and a
RNase P
/MRP-directed cleavage site upstream and downstream of the
YTHDF2
-binding site, respectively. We also find that a subset of m
6
A-containing circular RNAs associates with
YTHDF2
in an HRSP12-dependent manner and is selectively downregulated by
RNase P
/MRP. Thus, our data expand the known functions of
RNase P
/MRP to endoribonucleolytic cleavage of m
6
A RNAs.
...
PMID:Endoribonucleolytic Cleavage of m
6
A-Containing RNAs by RNase P/MRP Complex. 3093 54
N
6
-Methyladenosine (m
6
A), the most prevalent internal modification associated with eukaryotic mRNAs, influences many steps of mRNA metabolism, including splicing, export, and translation, as well as stability. Recent studies have revealed that m
6
A-containing mRNAs undergo one of two distinct pathways of rapid degradation: deadenylation via the YT521-B homology (YTH) domain-containing family protein 2 (
YTHDF2
; an m
6
A reader protein)-CCR4/NOT (deadenylase) complex or endoribonucleolytic cleavage by the
YTHDF2
-HRSP12-ribonuclease (RNase) P/mitochondrial RNA-processing (MRP) (endoribonuclease) complex. Some m
6
A-containing circular RNAs (circRNAs) are also subject to endoribonucleolytic cleavage by
YTHDF2
-HRSP12-
RNase P
/MRP. Here, we highlight recent progress on the molecular mechanisms underlying rapid mRNA degradation via m
6
A and describe our current understanding of the dynamic regulation of m
6
A-mediated mRNA decay through the crosstalk between m
6
A (or
YTHDF2
) and other cellular factors.
...
PMID:Molecular Mechanisms Driving mRNA Degradation by m
6
A Modification. 3196 9
