The stability of m6A-marked transcripts is linked to cell identity in planarians
Abstract
N 6-methyladenosine (m6A) is a prevalent internal modification of eukaryotic mRNA that influences transcript fate, including mRNA stability and cell-type-specific gene expression. However, the mechanisms underlying m6A-mediated regulation remain poorly understood in many systems, including the highly regenerative planarian Schmidtea mediterranea. To address this, we generated a high-confidence atlas of ∼72 200 m6A sites across the planarian transcriptome using multiplexed direct RNA sequencing. The m6A sites follow a DRAYW consensus motif and are highly enriched near stop codons while being largely excluded from coding sequences. This pattern aligns with an exon and intron length-dependent variant of the exon junction complex (EJC)-mediated exclusion model, wherein the EJC restricts m6A deposition near splice sites. Knockdown of the m6A writer complex induced pronounced, cell-type-specific changes in transcript stability. Destabilized transcripts were enriched for intestinal markers, whereas stabilized transcripts were associated with neoblasts, the adult stem cells of planarians. Transcriptional shut-off experiments confirmed that m6A has opposing effects on mRNA decay depending on cellular context: it stabilizes transcripts in differentiated cells, while it promotes the degradation of mRNAs associated with neoblasts. Collectively, these results support a model in which cell-type-specific regulation of mRNA stability by m6A plays a crucial role in shaping cell identity in planarians.
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BibTeX
@article{hohn2026stability,
title = {{The stability of m6A-marked transcripts is linked to cell identity in planarians}},
author = {Constantin Höhn and Andreas Pittroff and Anne-Sophie Gribling-Burrer and Lisa Hülsmann and Redmond Smyth and Claus-D Kuhn},
journal = {Nucleic Acids Research},
year = {2026},
month = sep,
doi = {10.1093/nar/gkag892},
url = {https://hal.science/hal-05791574v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The stability of m6A-marked transcripts is linked to cell identity in planarians
AU - Constantin Höhn
AU - Andreas Pittroff
AU - Anne-Sophie Gribling-Burrer
AU - Lisa Hülsmann
AU - Redmond Smyth
AU - Claus-D Kuhn
PY - 2026
DA - 2026/09/22
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag892
UR - https://hal.science/hal-05791574v1
AB - N 6-methyladenosine (m6A) is a prevalent internal modification of eukaryotic mRNA that influences transcript fate, including mRNA stability and cell-type-specific gene expression. However, the mechanisms underlying m6A-mediated regulation remain poorly understood in many systems, including the highly regenerative planarian Schmidtea mediterranea. To address this, we generated a high-confidence atlas of ∼72 200 m6A sites across the planarian transcriptome using multiplexed direct RNA sequencing. The m6A sites follow a DRAYW consensus motif and are highly enriched near stop codons while being largely excluded from coding sequences. This pattern aligns with an exon and intron length-dependent variant of the exon junction complex (EJC)-mediated exclusion model, wherein the EJC restricts m6A deposition near splice sites. Knockdown of the m6A writer complex induced pronounced, cell-type-specific changes in transcript stability. Destabilized transcripts were enriched for intestinal markers, whereas stabilized transcripts were associated with neoblasts, the adult stem cells of planarians. Transcriptional shut-off experiments confirmed that m6A has opposing effects on mRNA decay depending on cellular context: it stabilizes transcripts in differentiated cells, while it promotes the degradation of mRNAs associated with neoblasts. Collectively, these results support a model in which cell-type-specific regulation of mRNA stability by m6A plays a crucial role in shaping cell identity in planarians.
SN - 0305-1048
SN - 1362-4962
ER -