Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq

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.

doi:10.1038/s41587-024-02245-9

Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq

detalle del documento

IDENTIFICACIÓN

doi:10.1038/s41587-024-02245-9...

Autor

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

Editor

Nature

Categoría

Life Sciences

Año

2024

fecha de cotización

29/5/2024

Palabras clave

rna alzheimer human frontal

Métrico

Resumen

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