RPS3

Description

The RPS3 (ribosomal protein S3) is a protein-coding gene located on chromosome 11.

40S ribosomal protein S3 is a protein that in humans is encoded by the RPS3 gene.

== Function == Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit, where it forms part of the domain where translation is initiated. The protein belongs to the S3P family of ribosomal proteins. Studies of the mouse and rat proteins have demonstrated that the protein has an extraribosomal role as an endonuclease involved in the repair of UV-induced DNA damage. The protein appears to be located in both the cytoplasm and nucleus but not in the nucleolus. Higher levels of expression of this gene in colon adenocarcinomas and adenomatous polyps compared to adjacent normal colonic mucosa have been observed. This gene is co-transcribed with the small nucleolar RNA genes U15A and U15B, which are located in its first and fifth introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

RPS3, also known as 40S ribosomal protein S3, is a component of the small ribosomal subunit (PubMed:8706699, PubMed:23636399). It plays a crucial role in protein synthesis, a fundamental cellular process. RPS3 exhibits endonuclease activity and participates in DNA repair mechanisms (PubMed:7775413). It cleaves phosphodiester bonds in damaged DNA with broad specificity, preferentially targeting supercoiled DNA over relaxed DNA (PubMed:15707971). RPS3 demonstrates a high affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (PubMed:14706345). Interestingly, RPS3 binds to both intact and damaged DNA with similar affinity (PubMed:18610840). Furthermore, RPS3 stimulates the N-glycosylase activity of the base excision protein OGG1 (PubMed:15518571) and enhances the uracil excision activity of UNG1 (PubMed:18973764). It also promotes the cleavage of the phosphodiester backbone by APEX1 (PubMed:18973764). When localized to the mitochondrion, RPS3 effectively reduces cellular ROS levels and mitochondrial DNA damage (PubMed:23911537). However, it can also negatively regulate DNA repair in cells exposed to hydrogen peroxide (PubMed:17049931). RPS3 plays a significant role in regulating transcription as part of the NF-kappa-B p65-p50 complex. It binds to the RELA/p65 subunit, enhances the complex's binding to DNA, and promotes transcription of target genes (PubMed:18045535). Additionally, RPS3 represses its own translation by binding to its cognate mRNA (PubMed:20217897). RPS3 interacts with and protects TP53/p53 from MDM2-mediated ubiquitination (PubMed:19656744). RPS3 is involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (PubMed:23131551). It contributes to the induction of apoptosis by activating CASP8 (PubMed:14988002). RPS3 induces neuronal apoptosis by interacting with the E2F1 transcription factor, synergistically upregulating pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (PubMed:20605787). Following UV radiation exposure, RPS3 interacts with TRADD, triggering apoptosis through caspase-dependent JNK activation (PubMed:22510408).

RPS3 is also known as S3, uS3.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing