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Genomics. 2017 Mar;109(2):113-122. doi: 10.1016/j.ygeno.2017.01.001. Epub 2017 Jan 22.

Widespread pre-translational regulation of the inclusion of signal peptides in human proteins.

Author information

1
Department of Biochemistry and RNA Group, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1E 4K8, Canada.
2
Department of Biochemistry and RNA Group, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1E 4K8, Canada. Electronic address: michelle.scott@usherbrooke.ca.

Abstract

Signal peptides (SP) are cleavable N-terminal protein motifs used co-translationally for entry of nascent polypeptides into the secretory pathway. Their co-translational cleavage prevents their extensive post-translational regulation and flexibility in their usage is made possible by the control of their inclusion at a pre-translational level. To characterize this regulation on a transcriptome scale, we analyzed the level and mechanisms of inclusion of the 3298 most likely human SP-encoding genes, 47% of which alternatively express their SP. Analysis of RNA-seq data across different normal human tissues indicates that pre-translational regulation of the SP differs depending on tissue-coverage of the gene, with alternative SP genes more likely to be widely expressed than constitutive SP genes. SP inclusion represents a new metric to measure functional gene expression and its deregulation in disease. Our analysis supports the extensive use of pre-translational regulation of SP inclusion, with functional consequences and implications for biomarker discovery.

KEYWORDS:

Alternative splicing; Pre-translational regulation; Protein subcellular localization; RNA-seq; Signal peptide; Tissue-specific regulation

PMID:
28119109
DOI:
10.1016/j.ygeno.2017.01.001
[Indexed for MEDLINE]
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