New role of human ribosomal protein S3: Regulation of cell cycle via phosphorylation by cyclin-dependent kinase 2

Abstract

Human ribosomal protein S3 (hRpS3) is a component of the 40S ribosomal subunit that associated in protein synthesis. hRpS3 has additional ribosomal functions such as DNA repair, transcription, metastasis, and apoptosis via interaction with numerous signaling molecules and has different modifications. Cyclin-dependent kinases (CDKs) are heterodimeric serine/threonine protein kinases that regulate cell cycle progression. Among its members, the Cdk1-cyclin B complex is known to control cell progression in the G2/M phase, while Cdk2-cyclin E/A complexes function in G1/S and S/G2 transition. In our previous study, we observed interaction between hRpS3 and Cdk1. The present study investigated the interaction between hRpS3 and Cdk2. Cdk2 phosphorylated hRps3 at amino acid residues S6 and T221 during the S-phase. Furthermore, hRpS3 knockdown delayed cell cycle progression by modulating the expression of cell cycle-related proteins, including cyclin B1 and cyclin E1. These findings suggest that hRpS3 is involved in Cdk2-mediated cell cycle regulation.

The Ribosome as a Missing Link in Prebiotic Evolution III: Over-Representation of tRNA- and rRNA-Like Sequences and Plieofunctionality of Ribosome-Related Molecules Argues for the Evolution of Primitive Genomes from Ribosomal RNA Modules

“…We have previously reviewed evidence for autologous regulation of most ribosomal proteins of their own translation by means of binding directly to their own mRNA [7], and they include only a summary of that information in Table 3, Table 4, Table 5 and Table 6. The majority of ribosomal proteins, both in prokaryotes and eukaryotes, play additional roles in cellular metabolism, ranging from DNA repair, control of transcription and replication, and histone binding to the regulation of various enzymes and mRNA splicing as summarized in Table 3, Table 4, Table 5 and Table 6 [81,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112]. The degree to which these extra-ribosomal functions are integrated into cellular functions is exemplified by the participation of riboprotein L13a into the GAIT complex in eukaryotes.…”

SUMO Protease SMT7 Modulates Ribosomal Protein L30 and Regulates Cell-Size Checkpoint Function

“…The other possibility is that accumulation of SUMOylated RPL30 has an extra-ribosomal function. Many ribosomal proteins in plant and animal systems have been reported to have specialized functions other than translation (Warner and McIntosh, 2009;Nagaraj et al, 2015;Han et al, 2017;Li et al, 2017;Zhang et al, 2017;Dionne et al, 2019). Moreover, SUMO conjugation of mouse RPL11 protein has been shown to regulate p53-mediated stress responses (El Motiam et al, 2018), further supporting the importance of SUMOylation on the extraribosomal functions of ribosomal proteins.…”

Novel autoregulatory cases of alternative splicing coupled with nonsense-mediated mRNA decay

“…Studies in Caenorhabditis elegans have shown that it is not uncommon 332 among ribosomal proteins to be AS-NMD targets [25]. In particular, ribosomal proteins L3, L10a, and 333 L12 use an evolutionarily-conserved pathway to insert PTCs in their pre-mRNA [76][77][78]. Here we show 334 that exon 2 of RPS3 has an alternative upstream donor site that induces a frameshift and targets RPS3 335 pre-mRNA for degradation ( Figure 4c).…”

“…Human ribosomal protein S3 (RPS3) is a component of the 40S ribosomal subunit that is mainly associated 330 with protein synthesis. However, RPS3 has many additional extraribosomal functions and is involved in 331 apoptosis and tumorigenesis [76]. Studies in Caenorhabditis elegans have shown that it is not uncommon 332 among ribosomal proteins to be AS-NMD targets [25].…”