Unveiling alterative splice diversity from human oligodendrocyte proteome data

Author(s)

Tavares, Raphael ; Wajnberg, Gabriel ; Scherer, Nicole de Miranda ; Pauletti, Bianca Alves ; Cassoli, Juliana S. ; Ferreira, Carlos Gil ; Paes Leme, Adriana Franco ; de Araujo-Souza, Patricia Savio ; Martins-de-Souza, Daniel ; Passetti, Fabio

• Document type: Journal article
• Source: JOURNAL OF PROTEOMICS; v. 151, p. 9-pg., 2017-01-16.

Abstract

Oligodendrocytes produce and maintain the myelin sheath of axons in the central nervous system. Because misassembled myelin sheaths have been associated with brain disorders such as multiple sclerosis and schizophrenia, recent advances have been made towards the description of the oligodendrocyte proteome. The identification of splice variants represented in the proteome is as important as determining the level of oligodendrocyte-associated proteins. Here, we used an oligodendrocyte proteome dataset deposited in ProteomeXchange to search against a customized protein sequence file containing computationally predicted splice variants. Our approach resulted in the identification of 39 splice variants, including one variant from the GTPase KRAS gene and another from the human glutaminase gene family. We also detected the mRNA expression of five selected splice variants and demonstrated that a fraction of these have their canonical proteins participating in direct protein-protein interactions. In conclusion, we believe our findings contribute to the molecular characterization of oligodendrocytes and may encourage other research groups working with central nervous system disorders to investigate the biological significance of these splice variants. The splice variants identified in this study may encode proteins that could be targeted in novel treatment strategies and diagnostic methods. Significance: Several disorders of the central nervous system (CNS) are associated with misassembled myelin sheaths, which are produced and maintained by oligodendrocytes (OL). Recently, the OL proteome has been explored to identify key proteins and molecular functions associated with CNS disorders. We developed an innovative approach to select, with a higher level of confidence, a relevant list of splice variants from a proteome dataset and detected the mRNA expression of five selected variants: EEF1D, OAS, MFF, SDR39U1, and SUGT1. We also described splice variants extracted from OL proteome data. Among the splice variants identified, some are from genes previously linked to CNS and related disorders. Our findings may contribute to oligodendrocyte characterization and encourage other research groups to investigate the biological role of splice variants and to improve current treatments and diagnostic methods for CNS disorders. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 10/19278-0 - Study of regulation of ADAMs in oral cancer
• Grantee: Adriana Franco Paes Leme
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 09/54067-3 - Acquisition of a mass spectrometer coupled to a liquid chromatography system for increasing the capacity to meet the needs of users and for making new technologies available in the Laboratory of Mass Spectrometry
• Grantee: Adriana Franco Paes Leme
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/14881-1 - Understanding the influence of glycolysis components in the function of oligodendrocytes: linking with findings in schizophrenia
• Grantee: Juliana Silva Cassoli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Grants - Young Investigators Grants