Hepatitis, Testicular Degeneration, and Ataxia in DIDO3-deficient Mice with Altered MRNA Processing

Overview

Journal Cell Biosci

Publisher Biomed Central

Specialty Biology

Date 2022 Jun 7

PMID 35672775

Authors

Julio Gutierrez

Karel H M van Wely

Carlos Martinez-A

Affiliations

Soon will be listed here.

Abstract

Background: mRNA processing is an essential step of gene expression; its malfunction can lead to different degrees of physiological disorder from subclinical disease to death. We previously identified Dido1 as a stemness marker and a gene involved in embryonic stem cell differentiation. DIDO3, the largest protein encoded by the Dido1 gene, is necessary for accurate mRNA splicing and correct transcription termination. The deletion of Dido1 exon16, which encodes the carboxy-terminal half of DIDO3, results in early embryonic lethality in mouse.

Results: We obtained mice bearing a Cre-LoxP conditional version of that deletion and studied the effects of inducing it ubiquitously in adult stages. DIDO3-deficient mice survive the deletion but suffer mild hepatitis, testicular degeneration, and progressive ataxia, in association with systemic alterations in mRNA splicing and transcriptional readthrough.

Conclusions: These results offer insight into the distinct vulnerabilities in mouse organs following impairment of the mRNA processing machinery, and could aid understanding of human health dependence on accurate mRNA metabolism.

Citing Articles

The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation.

Benedum J, Franke V, Appel L, Walch L, Bruno M, Schneeweiss R Nat Commun. 2023; 14(1):7912.

PMID: 38036524 PMC: 10689479. DOI: 10.1038/s41467-023-43724-y.

SPOC domain proteins in health and disease.

Appel L, Benedum J, Engl M, Platzer S, Schleiffer A, Strobl X Genes Dev. 2023; 37(5-6):140-170.

PMID: 36927757 PMC: 10111866. DOI: 10.1101/gad.350314.122.

Correction to: Hepatitis, testicular degeneration, and ataxia in DIDO3-deficient mice with altered mRNA processing.

Gutierrez J, van Wely K, Martinez-A C Cell Biosci. 2022; 12(1):144.

PMID: 36056442 PMC: 9440595. DOI: 10.1186/s13578-022-00843-1.

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