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The m6A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5′–3′ exoribonuclease XRN1
- Source :
- RNA. 24:1339-1350
- Publication Year :
- 2018
- Publisher :
- Cold Spring Harbor Laboratory, 2018.
-
Abstract
- N6-methyladenosine (m6A) modifications in RNAs play important roles in regulating many different aspects of gene expression. While m6As can have direct effects on the structure, maturation, or translation of mRNAs, such modifications can also influence the fate of RNAs via proteins termed “readers” that specifically recognize and bind modified nucleotides. Several YTH domain-containing proteins have been identified as m6A readers that regulate the splicing, translation, or stability of specific mRNAs. In contrast to the other YTH domain-containing proteins, YTHDC2 has several defined domains and here, we have analyzed the contribution of these domains to the RNA and protein interactions of YTHDC2. The YTH domain of YTHDC2 preferentially binds m6A-containing RNAs via a conserved hydrophobic pocket, whereas the ankyrin repeats mediate an RNA-independent interaction with the 5′–3′ exoribonuclease XRN1. We show that the YTH and R3H domains contribute to the binding of YTHDC2 to cellular RNAs, and using crosslinking and analysis of cDNA (CRAC), we reveal that YTHDC2 interacts with the small ribosomal subunit in close proximity to the mRNA entry/exit sites. YTHDC2 was recently found to promote a “fast-track” expression program for specific mRNAs, and our data suggest that YTHDC2 accomplishes this by recruitment of the RNA degradation machinery to regulate the stability of m6A-containing mRNAs and by utilizing its distinct RNA-binding domains to bridge interactions between m6A-containing mRNAs and the ribosomes to facilitate their efficient translation.
- Subjects :
- 0301 basic medicine
RNA
Translation (biology)
Biology
Ribosome
Protein–protein interaction
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
030220 oncology & carcinogenesis
Exoribonuclease
RNA splicing
Gene expression
Ankyrin repeat
Molecular Biology
Subjects
Details
- ISSN :
- 14699001 and 13558382
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- RNA
- Accession number :
- edsair.doi...........2e6aee14a1bc8b6492a138eb378b54d0
- Full Text :
- https://doi.org/10.1261/rna.064238.117