RSL1D1 is a nucleolar protein that regulates mRNA translation (Ma et al., 2008).

By suppressive subtractive hybridization to identify proteins downregulated with replicative senescence in 2BS human diploid fibroblasts, followed by PCR amplification, Ma et al. (2008) cloned RSL1D1, which they called CSIG. The deduced 490-amino acid protein has an N-terminal ribosomal L1 (see MRPL1, 611821) domain and a C-terminal lysine-rich domain. Northern blot analysis detected variable CSIG expression in most human tissues examined, with highest expression in heart, skeletal muscle, and placenta, and little to no expression in brain, colon, and thymus. Endogenous CSIG localized predominantly to the nucleolus in 2BS and HeLa cells and fractionated with HEK293 cell polysomes. Western blot analysis detected CSIG at an apparent molecular mass of 55 kD.

Ma et al. (2008) determined that the RSL1D1 gene contains 9 exons and spans 5.1 kb.

Ma et al. (2008) reported that the RSL1D1 gene maps to chromosome 16p13.

UPA (PLAU; 191840) is an extracellular matrix protease involved in cell migration. Using a yeast 1-hybrid screen and EMSA, Tong et al. (2005) found that RSL1D1, or PBK1, bound an enhancer region in the UPA promoter between 2 AP1 (see 165160) sites. Overexpression and knockdown experiments with 95D human lung cancer cell lines confirmed that PBK1 upregulated UPA expression by binding to the enhancer element.

Ma et al. (2008) found that overexpression of CSIG in 2BS fibroblasts promoted cell growth, increased the number of cells in S phase, and delayed senescence. In contrast, silencing of CSIG via small interfering RNA delayed cell growth, decreased the number of cells in S and G2/M phases, and accelerated cellular senescence. Reporter gene assays and Western blot analysis revealed that CSIG negatively regulated PTEN (601728) and its downstream effector p27(KIP1) (CDKN1B; 600778), both of which are required for replicative senescence. Binding studies showed that CSIG interacted with a specific segment of the PTEN 5-prime UTR, possibly indirectly, and downregulated PTEN translation, resulting in p27(KIP1) destabilization. Expression of PTEN was essential for CSIG-dependent expression of p27(KIP1) and cell cycle progression.

Wang et al. (2023) downregulated Rsl1d1 expression in fertilized mouse oocytes at the 2-pronuclei (2PN) stage. Almost all of the Rsl1d1 knockdown embryos were arrested at the morula stage compared to controls, and Rsl1d1 cRNA injection rescued the phenotype. The authors then generated mice with oocyte-specific knockout of Rsl1d1 and observed that homozygous females were completely infertile. Most oocytes from the homozygous female mice could be fertilized normally, and approximately 65% of zygotes could develop to the 2-cell stage, but few of those were able to progress to the 4-cell stage. The authors noted that this phenotype exactly recapitulated that of Kpna2 (see 614107) -/- female mice. Immunoprecipitation studies in HEK293T cells showed that RSL1D1 is a downstream substrate of mouse Kpna2 and its human homolog KPNA7 (614107), suggesting that both exert their function through RSL1D1 during embryonic development.