title: Widespread pre-translational regulation of the inclusion of signal peptides in human proteins.
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.
authors.affiliation: Department of Biochemistry and RNA Group, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1E 4K8, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Balthazar
authors.affiliation: Department of Biochemistry and RNA Group, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1E 4K8, Canada.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Tucunduva
authors.affiliation: Department of Biochemistry and RNA Group, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1E 4K8, Canada.
authors.forename: Mikael-Jonathan
authors.initials: MJ
authors.lastname: Luce
authors.affiliation: 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.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Scott
mesh_terms: D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D009928:Organ Specificity; D021382:Protein Sorting Signals; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA
chemical_list: D021382:Protein Sorting Signals; D012333:RNA, Messenger
keywords: Alternative splicing; Pre-translational regulation; Protein subcellular localization; RNA-seq; Signal peptide; Tissue-specific regulation