Détail du document
Identifiant
doi:10.1038/s41587-024-02245-9...
Auteur
Aguzzoli Heberle, Bernardo Brandon, J. Anthony Page, Madeline L. Nations, Kayla A. Dikobe, Ketsile I. White, Brendan J. Gordon, Lacey A. Fox, Grant A. Wadsworth, Mark E. Doyle, Patricia H. Williams, Brittney A. Fox, Edward J. Shantaraman, Anantharaman Ryten, Mina Goodwin, Sara Ghiban, Elena Wappel, Robert Mavruk-Eskipehlivan, Senem Miller, Justin B. Seyfried, Nicholas T. Nelson, Peter T. Fryer, John D. Ebbert, Mark T. W.Langue
enEditeur
Nature
Catégorie
Life Sciences
Année
2024
Date de référencement
29/05/2024
Mots clés
rna alzheimer human frontalRésumé
The landscape of RNA isoforms in human cortex is revealed by deep long-read RNA sequencing.
Determining whether the RNA isoforms from medically relevant genes have distinct functions could facilitate direct targeting of RNA isoforms for disease treatment.
Here, as a step toward this goal for neurological diseases, we sequenced 12 postmortem, aged human frontal cortices (6 Alzheimer disease cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell per sample.
We identified 1,917 medically relevant genes expressing multiple isoforms in the frontal cortex where 1,018 had multiple isoforms with different protein-coding sequences.
Of these 1,018 genes, 57 are implicated in brain-related diseases including major depression, schizophrenia, Parkinson’s disease and Alzheimer disease.
Our study also uncovered 53 new RNA isoforms in medically relevant genes, including several where the new isoform was one of the most highly expressed for that gene.
We also reported on five mitochondrially encoded, spliced RNA isoforms.
We found 99 differentially expressed RNA isoforms between cases with Alzheimer disease and controls.
Aguzzoli Heberle, Bernardo,Brandon, J. Anthony,Page, Madeline L.,Nations, Kayla A.,Dikobe, Ketsile I.,White, Brendan J.,Gordon, Lacey A.,Fox, Grant A.,Wadsworth, Mark E.,Doyle, Patricia H.,Williams, Brittney A.,Fox, Edward J.,Shantaraman, Anantharaman,Ryten, Mina,Goodwin, Sara,Ghiban, Elena,Wappel, Robert,Mavruk-Eskipehlivan, Senem,Miller, Justin B.,Seyfried, Nicholas T.,Nelson, Peter T.,Fryer, John D.,Ebbert, Mark T. W., 2024, Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq, Nature
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