期刊
CELL REPORTS
卷 7, 期 3, 页码 735-746出版社
CELL PRESS
DOI: 10.1016/j.celrep.2014.03.053
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资金
- National Basic Research Program of China/973 [2011CB504200, 2012CB910700]
- National Natural Science Foundation of China [31171260, 81261120399, 81330054, J1103518]
- Science & Technology Department of Sichuan Province [2013JQ0041]
Primordial dwarfism (PD) is characterized by global growth failure, both during embryogenesis and postnatally. Loss-of-function germline mutations in La ribonucleoprotein domain family, member 7 (LAPR7) have recently been linked to PD. Paradoxically, LARP7 deficiency was previously assumed to be associated with increased cell growth and proliferation via activation of positive transcription elongation factor b (P-TEFb). Here, we show that Larp7 deficiency likely does not significantly increase P-TEFb activity. We further discover that Larp7 knockdown does not affect pluripotency but instead primes embryonic stem cells (ESCs) for differentiation via downregulation of Lin28, a positive regulator of organismal growth. Mechanistically, we show that Larp7 interacts with a poly(A) polymerase Star-PAP to maintain Lin28 mRNA stability. We propose that proper regulation of Lin28 and PTEFb is essential for embryonic cells to achieve a sufficient number of cell divisions prior to differentiation and ultimately to maintain proper organismal size.
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