Expression of Truncated Products at the 5′-Terminal Region of RIPK2 and Evolutive Aspects that Support Their Biological Importance

Abstract Alternative splicing is the process of generating different mRNAs from the same primary transcript, which contributes to increase the transcriptome and proteome diversity. Abnormal splicing has been associated with the development of several diseases including cancer. Given that mutations a...

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Published in:	Genome biology and evolution Vol. 16; no. 7
Main Authors:	Villagra, Ulises M M, da Cunha, Bianca R, Polachini, Giovana M, Henrique, Tiago, Stefanini, Ana Carolina Buzzo, de Castro, Tialfi Bergamin, da Silva, Carlos H T P, Feitosa, Olavo A, Fukuyama, Erica E, López, Rossana V M, Dias-Neto, Emmanuel, Nunes, Fabio D, Severino, Patricia, Tajara, Eloiza H
Format:	Journal Article
Language:	English
Published:	UK Oxford University Press 03-07-2024
Subjects:	Alternative splicing Isoforms Kinases N-Terminus Proteomes Transcriptomes isoform conservation RIP-2 alternative splicing stress conditions RIPK2 gene expression
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Summary:	Abstract Alternative splicing is the process of generating different mRNAs from the same primary transcript, which contributes to increase the transcriptome and proteome diversity. Abnormal splicing has been associated with the development of several diseases including cancer. Given that mutations and abnormal levels of the RIPK2 transcript and RIP-2 protein are frequent in tumors, and that RIP-2 modulates immune and inflammatory responses, we investigated alternative splicing events that result in partial deletions of the kinase domain at the N-terminus of RIP-2. We also investigated the structure and expression of the RIPK2 truncated variants and isoforms in different environments. In addition, we searched data throughout Supraprimates evolution that could support the biological importance of RIPK2 alternatively spliced products. We observed that human variants and isoforms were differentially regulated following temperature stress, and that the truncated transcript was more expressed than the long transcript in tumor samples. The inverse was found for the longer protein isoform. The truncated variant was also detected in chimpanzee, gorilla, hare, pika, mouse, rat, and tree shrew. The fact that the same variant has been preserved in mammals with divergence times up to 70 million years raises the hypothesis that it may have a functional significance.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Ulises M M Villagra, Bianca R da Cunha and Giovana M Polachini contributed equally to this work. Conflicts of Interest The authors declare no competing interests.
ISSN:	1759-6653 1759-6653
DOI:	10.1093/gbe/evae106