Authors
Egor A Smolin, Andrey I Buyan, Dmitry N Lyabin, Anton A Buzdin, Ivan V Kulakovskiy, Irina A Eliseeva
Published in
RNA (New York, N.Y.). Sep 17, 2026. Epub Sep 17, 2026.
Abstract
N⁶-methyladenosine (m⁶A) plays an important role in translation control and, particularly, in cap-independent initiation. The impact of m⁶A is usually studied in the context of its location in the transcripts, but the global impact of m⁶A along mRNAs remains unclear. Here, we combined ribosome profiling under conditions of mTOR inhibition and m⁶A mapping to identify distinct subsets of mRNAs that differ in their sensitivity to the suppression of cap-dependent initiation. We found that the sensitivity strongly correlated with the total m⁶A methylation of the transcripts. Further, upon decreased mTOR activity, m⁶A methylation facilitated the enhanced association of mRNAs with components of the eIF4F complex. Thus, the efficiency of cap-independent translation initiation is primarily defined not by precise localization but by the total level of m⁶A methylation, and m⁶A has a compensatory role in maintaining translation when the canonical cap-dependent pathway is impaired. Our findings underscore the significance of contemplating global m⁶A methylation status as a pivotal element in translational control, particularly under stress or signaling perturbations.
PMID:
42754366
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.
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