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

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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. ; Lopez, Rossana V. M. ; Dias-Neto, Emmanuel ; Nunes, Fabio D. ; Severino, Patricia ; Tajara, Eloiza H.

• Tipo de documento: Artigo Científico
• Fonte: GENOME BIOLOGY AND EVOLUTION; v. 16, n. 7, p. 20-pg., 2024-07-03.

Resumo

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. (AU)

• Processo FAPESP: 03/07802-3 - Analise de splicing alternativo utilizando dados de sequencias expressas.
• Beneficiário: Ulises Maximiliano Mancini Villagra
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/23353-0 - Estudo de proteínas glicosiladas e metabólitos em carcinoma epidermóide de cavidade oral
• Beneficiário: Giovana Mussi Polachini
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/51168-0 - Fatores ambientais, clínicos, histopatológicos e moleculares associados ao desenvolvimento e ao prognóstico de carcinomas epidermoides de cabeça e pescoço
• Beneficiário: Eloiza Helena Tajara da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/07293-0 - Perfil lipídico em Câncer de Cabeça e Pescoço
• Beneficiário: Tialfi Bergamin de Castro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/06048-2 - Análise do secretoma de carcinoma de cabeça e pescoço e de seu efeito no microambiente tumoral
• Beneficiário: Bianca Rodrigues da Cunha
• Modalidade de apoio: Bolsas no Brasil - Doutorado