Abstract
Simple SummaryRBM22 is a gene that encodes an essential RNA-Binding Protein involved in pre-mRNA splicing and transcription, with a DNA-binding function. This dual RNA/DNA-Binding activity provides a new insight of the regulation of gene expression by RBM22. Many studies have reported that RBM22 is essential for cell survival, mitosis, and differentiation processes. Consequently, RBM22 alterations are observed in several diseases and notably in cancer. It is suggested that RBM22 haploinsufficiency and dosage may be critical for its proper function. In this review, we aim at making a state-of-the-art review of this intriguing gene, encoding an RNA/DNA-binding protein that is understudied, and that could represent a potential therapeutic target in specific diseases and cancer.RNA-Binding Proteins (RBP) are very diverse and cover a large number of functions in the cells. This review focuses on RBM22, a gene encoding an RBP and belonging to the RNA-Binding Motif (RBM) family of genes. RBM22 presents a Zinc Finger like and a Zinc Finger domain, an RNA-Recognition Motif (RRM), and a Proline-Rich domain with a general structure suggesting a fusion of two yeast genes during evolution: Cwc2 and Ecm2. RBM22 is mainly involved in pre-mRNA splicing, playing the essential role of maintaining the conformation of the catalytic core of the spliceosome and acting as a bridge between the catalytic core and other essential protein components of the spliceosome. RBM22 is also involved in gene regulation, and is able to bind DNA, acting as a bona fide transcription factor on a large number of target genes. Undoubtedly due to its wide scope in the regulation of gene expression, RBM22 has been associated with several pathologies and, notably, with the aggressiveness of cancer cells and with the phenotype of a myelodysplastic syndrome. Mutations, enforced expression level, and haploinsufficiency of RBM22 gene are observed in those diseases. RBM22 could represent a potential therapeutic target in specific diseases, and, notably, in cancer.
Highlights
Proposed to be the first genetic-information carrier for the history of life [1], ribonucleic acids (RNA) are one of the most important molecules—if not the most important—in every living organism
It is important to note that many RNA-Binding Proteins (RBP) are able to contact several types of RNA at a time due to an important feature: most of them bear more than one RNA-Binding Domain (RBD) in their structure
We focus on the cellular and molecular functions of RBM22, due to its crucial role in pre-mRNA splicing
Summary
Proposed to be the first genetic-information carrier for the history of life [1], ribonucleic acids (RNA) are one of the most important molecules—if not the most important—in every living organism. Numerous RBDs are involved in the binding to a large variety of types and secondary structures of RNA. It is important to note that many RBPs are able to contact several types of RNA at a time due to an important feature: most of them bear more than one RBD in their structure. It can either be a repetition of the same RBD, or other types of RBDs [7]. RBM22 is a gene encoding an RBP that is mostly involved in pre-mRNA splicing, which has been, for a long time, understudied. We aim at making a state-of-the-art review of the current knowledge about RBM22, from its normal function to its pathological role
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