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Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Beyond microsatellite instability : intrinsic disorder as a potential link between protein short tandem repeats and cancer
Authors: Verbiest, Max
Delucchi, Matteo
Bilgin Sonay, Tugce
Anisimova, Maria
et. al: No
DOI: 10.3389/fbinf.2021.685844
Published in: Frontiers in Bioinformatics
Volume(Issue): 1
Issue: 685844
Issue Date: 8-Jun-2021
Publisher / Ed. Institution: Frontiers Research Foundation
ISSN: 2673-7647
Language: English
Subjects: Short tandem repeats; Microsatellites; Microsatellite instability; Intrinsic disorder; Cancer; Computational biology; Protein bioinformatics
Subject (DDC): 572: Biochemistry
Abstract: Short tandem repeats (STRs) are abundant in genomic sequences and are known for comparatively high mutation rates; STRs therefore are thought to be a potent source of genetic diversity. In protein-coding sequences STRs primarily encode disorder-promoting amino acids and are often located in intrinsically disordered regions (IDRs). STRs are frequently studied in the scope of microsatellite instability (MSI) in cancer, with little focus on the connection between protein STRs and IDRs. We believe, however, that this relationship should be explicitly included when ascertaining STR functionality in cancer. Here we explore this notion using all canonical human proteins from SwissProt, wherein we detected 3,699 STRs. Over 80% of these consisted completely of disorder promoting amino acids. 62.1% of amino acids in STR sequences were predicted to also be in an IDR, compared to 14.2% for non-repeat sequences. Over-representation analysis showed STR-containing proteins to be primarily located in the nucleus where they perform protein- and nucleotide-binding functions and regulate gene expression. They were also enriched in cancer-related signaling pathways. Furthermore, we found enrichments of STR-containing proteins among those correlated with patient survival for cancers derived from eight different anatomical sites. Intriguingly, several of these cancer types are not known to have a MSI-high (MSI-H) phenotype, suggesting that protein STRs play a role in cancer pathology in non MSI-H settings. Their intrinsic link with IDRs could therefore be an attractive topic of future research to further explore the role of STRs and IDRs in cancer. We speculate that our observations may be linked to the known dosage-sensitivity of disordered proteins, which could hint at a concentration-dependent gain-of-function mechanism in cancer for proteins containing STRs and IDRs.
Fulltext version: Published version
License (according to publishing contract): CC BY 4.0: Attribution 4.0 International
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Computational Life Sciences (ICLS)
Published as part of the ZHAW project: Trans-omic approach to colorectal cancer: an integrative computational and clinical perspective
Appears in collections:Publikationen Life Sciences und Facility Management

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