Matches in SemOpenAlex for { <https://semopenalex.org/work/W3040761286> ?p ?o ?g. }
- W3040761286 abstract "Ribosomopathies are congenital disorders caused by mutations in the genes encoding ribosomal and other functionally related proteins. They are characterized by anemia, other hematopoietic and developmental abnormalities, and p53 activation. Ribosome assembly requires coordinated expression of many ribosomal protein (RP) genes; however, the regulation of RP gene expression, especially in hematopoietic stem cells (HSCs), remains poorly understood. MYSM1 is a transcriptional regulator essential for HSC function and hematopoiesis. We established that HSC dysfunction in Mysm1 deficiency is driven by p53; however, the mechanisms of p53 activation remained unclear. Here, we describe the transcriptome of Mysm1-deficient mouse HSCs and identify MYSM1 genome-wide DNA binding sites. We establish a direct role for MYSM1 in RP gene expression and show a reduction in protein synthesis in Mysm1–/– HSCs. Loss of p53 in mice fully rescues Mysm1–/– anemia phenotype but not RP gene expression, indicating that RP gene dysregulation is a direct outcome of Mysm1 deficiency and an upstream mediator of Mysm1–/– phenotypes through p53 activation. We characterize a patient with a homozygous nonsense MYSM1 gene variant, and we demonstrate reduced protein synthesis and increased p53 levels in patient hematopoietic cells. Our work provides insights into the specialized mechanisms regulating RP gene expression in HSCs and establishes a common etiology of MYSM1 deficiency and ribosomopathy syndromes." @default.
- W3040761286 created "2020-07-16" @default.
- W3040761286 creator A5001276775 @default.
- W3040761286 creator A5004720947 @default.
- W3040761286 creator A5006442726 @default.
- W3040761286 creator A5010017790 @default.
- W3040761286 creator A5013067369 @default.
- W3040761286 creator A5019044095 @default.
- W3040761286 creator A5019745268 @default.
- W3040761286 creator A5023076435 @default.
- W3040761286 creator A5030054330 @default.
- W3040761286 creator A5043461617 @default.
- W3040761286 creator A5043654086 @default.
- W3040761286 creator A5045348393 @default.
- W3040761286 creator A5060693519 @default.
- W3040761286 creator A5065502457 @default.
- W3040761286 creator A5077350103 @default.
- W3040761286 date "2020-07-09" @default.
- W3040761286 modified "2023-09-27" @default.
- W3040761286 title "MYSM1 maintains ribosomal protein gene expression in hematopoietic stem cells to prevent hematopoietic dysfunction" @default.
- W3040761286 cites W1628442568 @default.
- W3040761286 cites W1808711893 @default.
- W3040761286 cites W1881873400 @default.
- W3040761286 cites W1895643351 @default.
- W3040761286 cites W1967551291 @default.
- W3040761286 cites W1968345969 @default.
- W3040761286 cites W1968492615 @default.
- W3040761286 cites W1974182237 @default.
- W3040761286 cites W1979594866 @default.
- W3040761286 cites W1979873360 @default.
- W3040761286 cites W1989561383 @default.
- W3040761286 cites W1990976022 @default.
- W3040761286 cites W1992307025 @default.
- W3040761286 cites W1995091371 @default.
- W3040761286 cites W2011109198 @default.
- W3040761286 cites W2014677321 @default.
- W3040761286 cites W2019828567 @default.
- W3040761286 cites W2029058486 @default.
- W3040761286 cites W2029344766 @default.
- W3040761286 cites W2031017387 @default.
- W3040761286 cites W2035307976 @default.
- W3040761286 cites W2039516373 @default.
- W3040761286 cites W2040118243 @default.
- W3040761286 cites W2044745732 @default.
- W3040761286 cites W2044865769 @default.
- W3040761286 cites W2045405560 @default.
- W3040761286 cites W2045998598 @default.
- W3040761286 cites W2049831767 @default.
- W3040761286 cites W2055381702 @default.
- W3040761286 cites W2058097237 @default.
- W3040761286 cites W2059233607 @default.
- W3040761286 cites W2060870400 @default.
- W3040761286 cites W2069835655 @default.
- W3040761286 cites W2070154483 @default.
- W3040761286 cites W2070809783 @default.
- W3040761286 cites W2074670317 @default.
- W3040761286 cites W2074928689 @default.
- W3040761286 cites W2079368976 @default.
- W3040761286 cites W2079842788 @default.
- W3040761286 cites W2079918544 @default.
- W3040761286 cites W2080506902 @default.
- W3040761286 cites W2084104969 @default.
- W3040761286 cites W2088859314 @default.
- W3040761286 cites W2089736373 @default.
- W3040761286 cites W2097065948 @default.
- W3040761286 cites W2097795961 @default.
- W3040761286 cites W2103121534 @default.
- W3040761286 cites W2107018762 @default.
- W3040761286 cites W2116185766 @default.
- W3040761286 cites W2117131162 @default.
- W3040761286 cites W2121533623 @default.
- W3040761286 cites W2124985265 @default.
- W3040761286 cites W2130410032 @default.
- W3040761286 cites W2131271579 @default.
- W3040761286 cites W2132051882 @default.
- W3040761286 cites W2132392209 @default.
- W3040761286 cites W2133832061 @default.
- W3040761286 cites W2138207763 @default.
- W3040761286 cites W2140729960 @default.
- W3040761286 cites W2141455745 @default.
- W3040761286 cites W2157830903 @default.
- W3040761286 cites W2162544653 @default.
- W3040761286 cites W2163298748 @default.
- W3040761286 cites W2171808845 @default.
- W3040761286 cites W2190061239 @default.
- W3040761286 cites W2198414929 @default.
- W3040761286 cites W2214327922 @default.
- W3040761286 cites W2234708228 @default.
- W3040761286 cites W2256016639 @default.
- W3040761286 cites W2325112174 @default.
- W3040761286 cites W2413123002 @default.
- W3040761286 cites W2515329095 @default.
- W3040761286 cites W2552413775 @default.
- W3040761286 cites W2558126370 @default.
- W3040761286 cites W2568063219 @default.
- W3040761286 cites W2570488943 @default.
- W3040761286 cites W2577080295 @default.
- W3040761286 cites W2625763766 @default.
- W3040761286 cites W2765462681 @default.
- W3040761286 cites W2773619385 @default.