Year: 2024
Type: preprint
Abstract: N 6 ,2’- O -dimethyladenosine (m 6 Am) is a modified nucleotide located at the first transcribed position in mRNA and snRNA that is essential for diverse physiological processes. m 6 Am mapping methods assume each gene uses a single start nucleotide. However, gene transcription usually involves multiple start sites, generating numerous 5’ isoforms. Thus, gene-level annotations cannot capture the diversity of m 6 Am modification in the transcriptome. Here, we describe CROWN-seq, which simultaneously identifies transcription-start nucleotides and quantifies m 6 Am stoichiometry for each 5’ isoform that initiates with adenosine. Using CROWN-seq, we map the m 6 Am landscape in nine human cell lines. Our findings reveal that m 6 Am is nearly always a high stoichiometry modification, with only a small subset of cellular mRNAs showing lower m 6 Am stoichiometry. We find that m 6 Am is associated with increased transcript expression and provide evidence that m 6 Am may be linked to transcription initiation associated with specific promoter sequences and initiation mechanisms. These data suggest a potential new function for m 6 Am in influencing transcription.
Source: eLife
DOI: 10.7554/elife.104139
Authors: Jianheng Fox Liu, Ben R Hawley, Luke S Nicholson, Samie R Jaffrey
Institutions: Cornell University, Weill Cornell Medicine, Engage
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Institutes of Health, Centers for Disease Control and Prevention, Weill Cornell Medical College, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Institute of Neurological Disorders and Stroke
Awards: G2540252108, G2948991722, G5238100983, Ultra-sensitive multi-mode laser-scanning imaging system, G7698101757, G8917726039, G9000104524, G9000334407, New mechanisms and technologies for understanding post-transcriptional gene regulation in neurons, Molecular mechanisms and functions underlying the role of Fto in mu opioid actions
OpenAlex ID: W4405111053