Intrinsically Unstructured Sequences in the mRNA 3' UTR Reduce the Ability of Poly(A) Tail to Enhance Translation.
J Mol Biol
; 434(24): 167877, 2022 12 30.
Article
in En
| MEDLINE
| ID: mdl-36368412
ABSTRACT
The 5' cap and 3' poly(A) tail of mRNA are known to synergistically stimulate translation initiation via the formation of the capâ¢eIF4Eâ¢eIF4Gâ¢PABPâ¢poly(A) complex. Most mRNA sequences have an intrinsic propensity to fold into extensive intramolecular secondary structures that result in short end-to-end distances. The inherent compactness of mRNAs might stabilize the capâ¢eIF4Eâ¢eIF4Gâ¢PABPâ¢poly(A) complex and enhance cap-poly(A) translational synergy. Here, we test this hypothesis by introducing intrinsically unstructured sequences into the 5' or 3' UTRs of model mRNAs. We found that the introduction of unstructured sequences into the 3' UTR, but not the 5' UTR, decreases mRNA translation in cell-free wheat germ and yeast extracts without affecting mRNA stability. The observed reduction in protein synthesis results from the diminished ability of the poly(A) tail to stimulate translation. These results suggest that base pair formation by the 3' UTR enhances the cap-poly(A) synergy in translation initiation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Poly A
/
Protein Biosynthesis
/
3' Untranslated Regions
Type of study:
Prognostic_studies
Language:
En
Journal:
J Mol Biol
Year:
2022
Document type:
Article
Affiliation country:
United States