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Series GSE234223 Query DataSets for GSE234223
Status Public on Dec 12, 2024
Title Transposable element exonization by non-canonical splicing generates a diversity reservoir of functional protein isoforms
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Other
Summary mRNA splicing enlarges the diversity of the protein repertoire, mainly through alternative exon retention or skipping. Although non-canonical splicing variants that exonize intronic regions were recently identified at the mRNA level, their contribution to the cellular proteome remains unclear. Here, we describe a population of 1300 unannotated protein isoforms generated by non-canonical splicing between exons and transposable elements (TE) using a combination of transcriptome assembly, ribosome profiling, and mass spectrometry. Despite being shorter and expressed at lower levels, their translation efficiency is similar to that of canonical isoforms, and they are shared between individuals. Functional analyses of 5 different non-canonical isoforms show stable expression, specific intracellular localization, and modified functions, as compared to the corresponding canonical isoforms. Non-canonical isoforms derive mainly from evolutionarily ancient genes and are a preferential source of alternative splicing upon which natural selection can act. We conclude that recently exonized TE isoforms are potentially functional and represent a diversity reservoir of novel protein isoforms.
 
Overall design RNA-seq from from human cancer cell lines (treated or untreated with puromycin) used for transcriptome assembly. Differential expression analysis on cell lines overexpressing PTEN and WWOX non-canonical isoforms. Ribosome profiling in lung cancer cell lines. Differential expression analysis on cell lines for the study of non-canonical isoforms.
Web link https://doi.org/10.1016/j.cell.2024.11.011
 
Contributor(s) Arribas Y, Amigorena S
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Submission date Jun 06, 2023
Last update date Dec 13, 2024
Contact name Yago A Arribas
E-mail(s) yago.arribas-de-sandoval@curie.fr
Organization name Institut Curie
Street address 26 rue d'Ulm
City Paris
ZIP/Postal code 75005
Country France
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (106)
GSM7457556 H1650, untreated, rep 0
GSM7457557 MCF7, untreated, rep 0
GSM7457558 MDA-MB-231, untreated, rep 0
Relations
BioProject PRJNA980573

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE234223_RAW.tar 603.5 Mb (http)(custom) TAR (of GTF, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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