Hui Xian Poh Created 2026-10-20 Updated 2026-11-05
Coauthor of research on METTL3 transcript variants. The study investigated alternative splicing as an explanation for apparently METTL3-independent RNA methylation, showing why a genetic perturbation must be checked for residual functional products.[ref]
METTL3 Created 2026-10-20 Updated 2026-11-05
METTL3 is a catalytic component of a protein complex that deposits N6-methyladenosine on RNA, especially messenger RNA. It works with METTL14 and regulatory components rather than determining every cellular methylation site in isolation. Modification can affect RNA processing, stability or biological translation through proteins that recognize the mark. The effect of a METTL3 perturbation therefore depends on which transcripts and readers are present. [ref]
UniProtKB by the UniProt Consortium. Q86U44, Function, Catalytic activity and Subunit structure
It is a useful depletion control, but not an automatically modification-free negative control. A nominal knockout may retain functional products, and loss of one writer does not establish absence of every relevant RNA modification. Calling the sample completely negative requires independent validation of the molecular state being used as ground truth.
This distinction has direct experimental support: alternatively spliced functional METTL3 products have been found in some nominal knockout lines.[ref]
Alternative splicing of METTL3 explains apparently METTL3-independent m6A modifications in mRNA by Hui Xian Poh and others. Abstract and Results: residual functional METTL3 isoforms in purported knockout cells
That result identifies a possible failure mode; it does not prove that this particular sample has the same defect. A modification-free reference preparation and an independent chemical measurement would strengthen the interpretation.