RBM4

Description

The RBM4 (RNA binding motif protein 4) is a protein-coding gene located on chromosome 11.

RNA-binding protein 4 is a protein that in humans is encoded by the RBM4 gene. RBM4 is a protein categorized as an RNA recognition motif (RRM). RRM proteins represent a substantial and functionally varied category of RNA-binding proteins, participating in various functions such as RNA processing and transport, the control of RNA stability, and translational regulation. The RBM4 protein also can be recognized as Lark. Over the past five years, data has emerged from investigations involving mammalian cells, providing a clearer understanding of RBM4's functions. It is now evident that RBM4 serves as an RNA-binding protein, participating in a wide array of cellular processes, which encompass the alternative splicing of pre-mRNA, translation control, and RNA silencing. Structurally, RBM4 shares similarities with other RNA-binding proteins, featuring two RNA recognition motifs and a CCHC-type zinc finger. Notably, RBM4 demonstrates a high degree of conservation throughout the process of evolution. In the context of the human RBM4 gene, it shares an impressive 95% similarity with its murine counterpart.

== Structure == Within the realm of mammals, the two distinct isoforms of RBM4 are RBM4a and RBM4b.

RBM4, also known as Lark, is an RNA-binding protein involved in various cellular processes, including alternative splicing of pre-mRNA and translation regulation. It influences alternative 5'-splice site and exon selection, acting as a muscle cell differentiation-promoting factor. During muscle cell differentiation, RBM4 activates exon skipping of the PTB pre-mRNA and antagonizes the activity of the splicing factor PTBP1 to modulate muscle cell-specific exon selection of alpha tropomyosin. It binds to intronic pyrimidine-rich sequences in the TPM1 and MAPT pre-mRNAs and is required for the translational activation of PER1 mRNA in response to the circadian clock. RBM4 binds directly to the 3'-UTR of the PER1 mRNA and exerts a suppressive activity on Cap-dependent translation by binding to CU-rich responsive elements within the 3'UTR of mRNAs, a process enhanced under stress conditions or during myocyte differentiation. It recruits EIF4A1 to stimulate IRES-dependent translation initiation in response to cellular stress and associates with internal ribosome entry segments (IRES) in target mRNA species under stress conditions. RBM4 plays a role in miRNA-guided RNA cleavage and translation suppression by promoting the association of AGO2-containing miRNPs with their cognate target mRNAs and associates with miRNAs during muscle cell differentiation. In vitro, RBM4 preferentially binds to the 5'-CGCGCG[GCA]-3' motif.

RBM4 is also known as LARK, RBM4A, ZCCHC21, ZCRB3A.

Associated Diseases

WES Whole Exome Sequencing