Journal
CELL REPORTS
Volume 20, Issue 5, Pages 1229-1241Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.07.025
Keywords
-
Categories
Funding
- EMBL
- NIH [U01CA152813]
- ERC [AdG-670821]
- Swiss National Science Foundation [31003A_166435]
- SystemsX.ch through project PhosphonetX-PPM
- UK Medical Research Council [G1001521, G1001522, 4050551988]
- NHMRC [1127745]
- VESKI
- Cancer Research UK [22231] Funding Source: researchfish
- Medical Research Council [G1001521, G1001522, MC_UU_12022/1] Funding Source: researchfish
- Swiss National Science Foundation (SNF) [31003A_166435] Funding Source: Swiss National Science Foundation (SNF)
- MRC [MC_UU_12022/1, G1001521, G1001522] Funding Source: UKRI
- National Health and Medical Research Council of Australia [1127745] Funding Source: NHMRC
Ask authors/readers for more resources
Alternative splicing is a critical determinant of genome complexity and, by implication, is assumed to engender proteomic diversity. This notion has not been experimentally tested in a targeted, quantitative manner. Here, we have developed an integrative approach to ask whether perturbations in mRNA splicing patterns alter the composition of the proteome. We integrate RNA sequencing (RNA-seq) (to comprehensively report intron retention, differential transcript usage, and gene expression) with a data-independent acquisition (DIA) method, SWATH-MS (sequential window acquisition of all theoretical spectra-mass spectrometry), to capture an unbiased, quantitative snapshot of the impact of constitutive and alternative splicing events on the proteome. Whereas intron retention is accompanied by decreased protein abundance, alterations in differential transcript usage and gene expression alter protein abundance proportionate to transcript levels. Our findings illustrate how RNA splicing links isoform expression in the human transcriptome with proteomic diversity and provides a foundation for studying perturbations associated with human diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available