A formyl axis links metabolism to translation.

Authors

Christof Niehrs

Published in

Trends in biochemical sciences. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Initiator methionine tRNA is a key regulator of translation and cell growth. Recent work places formyl chemistry as a regulatory nexus across three molecular layers. In the protein layer, N-formylmethionine supports initiator tRNA recognition and stress-responsive proteostasis pathways. In the RNA layer, 5-formylcytidine at C34 of mitochondrial tRNA^Met expands AUG/AUA decoding. In the DNA layer, 5-formylcytosine activates polymerase III transcription of tRNA_i^Met gene clusters during frog zygotic genome activation. Despite distinct formylation routes and readouts, these layers converge on translational regulation and share metabolic dependencies. One-carbon metabolism supplies methyl/formyl precursors, while mitochondrial and oxidative states influence formyl-mark installation through redox balance and α-ketoglutarate-dependent dioxygenase activity. Together, these layers suggest a formyl-dependent rheostat linking metabolic state to translation capacity.

PMID:
42629223
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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