Similar Datasets
Project description:Oncogene-induced senescence is an important tumor suppressor mechanism that limits proliferation of cells harboring oncogenic mutations. Through a genome-wide screen, we discovered a conserved snoRNA, SNORA13, that is required for this pathway. Although SNORA13 guides the pseudouridylation of a highly conserved nucleotide in the ribosomal decoding center, loss of this snoRNA minimally impacts translation. Instead, we found that SNORA13 negatively regulates ribosome biogenesis. Oncogenic stress perturbs ribosome biogenesis, resulting in the accumulation of free ribosomal proteins (RPs) that trigger p53 activation. We showed that SNORA13 interacts directly with RPL23, decreasing its incorporation into maturing 60S subunits and, consequently, increasing the pool of free RPs, thereby promoting the p53-mediated senescence program. Thus, SNORA13 regulates ribosome biogenesis and the p53 pathway through a non-canonical mechanism distinct from its role in guiding RNA modification. These findings expand our understanding of snoRNA functions and the roles of these abundant noncoding RNAs in cellular signaling.
2024-07-01 | GSE232858 | GEO
Project description:Oncogene-induced senescence is an important tumor suppressor mechanism that limits proliferation of cells harboring oncogenic mutations. Through a genome-wide screen, we discovered a conserved snoRNA, SNORA13, that is required for this pathway. Although SNORA13 guides the pseudouridylation of a highly conserved nucleotide in the ribosomal decoding center, loss of this snoRNA minimally impacts translation. Instead, we found that SNORA13 negatively regulates ribosome biogenesis. Oncogenic stress perturbs ribosome biogenesis, resulting in the accumulation of free ribosomal proteins (RPs) that trigger p53 activation. We showed that SNORA13 interacts directly with RPL23, decreasing its incorporation into maturing 60S subunits and, consequently, increasing the pool of free RPs, thereby promoting the p53-mediated senescence program. Thus, SNORA13 regulates ribosome biogenesis and the p53 pathway through a non-canonical mechanism distinct from its role in guiding RNA modification. These findings expand our understanding of snoRNA functions and the roles of these abundant noncoding RNAs in cellular signaling.
2024-07-01 | GSE232856 | GEO
Project description:Oncogene-induced senescence is an important tumor suppressor mechanism that limits proliferation of cells harboring oncogenic mutations. Through a genome-wide screen, we discovered a conserved snoRNA, SNORA13, that is required for this pathway. Although SNORA13 guides the pseudouridylation of a highly conserved nucleotide in the ribosomal decoding center, loss of this snoRNA minimally impacts translation. Instead, we found that SNORA13 negatively regulates ribosome biogenesis. Oncogenic stress perturbs ribosome biogenesis, resulting in the accumulation of free ribosomal proteins (RPs) that trigger p53 activation. We showed that SNORA13 interacts directly with RPL23, decreasing its incorporation into maturing 60S subunits and, consequently, increasing the pool of free RPs, thereby promoting the p53-mediated senescence program. Thus, SNORA13 regulates ribosome biogenesis and the p53 pathway through a non-canonical mechanism distinct from its role in guiding RNA modification. These findings expand our understanding of snoRNA functions and the roles of these abundant noncoding RNAs in cellular signaling.
2024-07-01 | GSE232857 | GEO
Project description:A non-canonical role for a small nucleolar RNA in ribosome biogenesis and senescence
| PRJNA974100 | ENA
Project description:A non-canonical role for a small nucleolar RNA in ribosome biogenesis and senescence (Ribosome profiling)
| PRJNA974150 | ENA
Project description:A non-canonical role for a small nucleolar RNA in ribosome biogenesis and senescence (RNA-sequencing)
| PRJNA974151 | ENA
Project description:A non-canonical role for a small nucleolar RNA in ribosome biogenesis and senescence (CRISPRi screen)
| PRJNA974148 | ENA
Project description:SEC23B is a component of coat protein complex II (COPII) vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. Loss-of-function SEC23B mutations cause a rare form of anemia, resulting from decreased SEC23B levels. We recently identified germline heterozygous SEC23B variants as potentially cancer-predisposing. Mutant SEC23B associated with ER stress-mediated tumorigenesis, without decreased SEC23B expression. However, our understanding of the processes behind these observations remain limited. Here, we show mutant SEC23B exists within nucleoli, in addition to classical distribution at the ER/Golgi. This occurs independent of other COPII proteins and does not compromise secretory function. Mutant cells have increased ribosomal protein and translation-related gene expression, and enhanced translational capacity, in the presence of ER stress. We show that mutant SEC23B binds to UBF transcription factor, with increased UBF transcription factor binding at the ribosomal DNA promoter. Our data indicate SEC23B has potential non-canonical COPII-independent function, particularly within the ribosome biogenesis pathway, and that may contribute to the pathogenesis of cancer-predisposition.
| S-EPMC6121187 | biostudies-literature
Project description:Nucleostemin is a nucleolar GTP-binding protein that is involved in stem cell proliferation, embryonic development, and ribosome biogenesis in mammals. Plant nucleostemin-like 1 (NSN1) plays a role in embryogenesis, and apical and floral meristem development. In this study, a nucleolar function of NSN1 in the regulation of ribosome biogenesis was identified. Green fluorescent protein (GFP)-fused NSN1 localized to the nucleolus, which was primarily determined by its N-terminal domain. Recombinant NSN1 and its N-terminal domain (NSN1-N) bound to RNA in vitro. Recombinant NSN1 expressed GTPase activity in vitro. NSN1 silencing in Arabidopsis thaliana and Nicotiana benthamiana led to growth retardation and premature senescence. NSN1 interacted with Pescadillo and EBNA1 binding protein 2 (EBP2), which are nucleolar proteins involved in ribosome biogenesis, and with several ribosomal proteins. NSN1, NSN1-N, and EBP2 co-fractionated primarily with the 60S ribosomal large subunit in vivo. Depletion of NSN1 delayed 25S rRNA maturation and biogenesis of the 60S ribosome subunit, and repressed global translation. NSN1-deficient plants exhibited premature leaf senescence, excessive accumulation of reactive oxygen species, and senescence-related gene expression. Taken together, these results suggest that NSN1 plays a crucial role in plant growth and senescence by modulating ribosome biogenesis.
| S-EPMC4588883 | biostudies-literature
Project description:The small nucleolar RNA snR30 (U17 in humans) plays a unique role during ribosome synthesis. Unlike most members of the H/ACA class of guide RNAs, the small nucleolar ribonucleoprotein (snoRNP) complex assembled on snR30 does not direct pseudouridylation of ribosomal RNA (rRNA), but instead snR30 is critical for 18S rRNA processing during formation of the small subunit (SSU) of the ribosome. Specifically, snR30 is essential for three pre-rRNA cleavages at the A0/01, A1/1, and A2/2a sites in yeast and humans, respectively. Accordingly, snR30 is the only essential H/ACA guide RNA in yeast. Here, we summarize our current knowledge about the interactions and functions of snR30, discuss what remains to be elucidated, and present two non-exclusive hypotheses on the possible molecular function of snR30 during ribosome biogenesis. First, snR30 might be responsible for recruiting other proteins including endonucleases to the SSU processome. Second, snR30 may contribute to the refolding of pre-rRNA into a required conformation that serves as a checkpoint during ribosome biogenesis facilitating pre-rRNA cleavage. In both scenarios, the snR30 snoRNP may have scaffolding and RNA chaperoning activity. In conclusion, the snR30 snoRNP is a crucial player with an unknown molecular mechanism during ribosome synthesis, posing many interesting future research questions.
| S-EPMC7601244 | biostudies-literature