TY - JOUR
T1 - CNOT3 contributes to early B cell development by controlling Igh rearrangement and p53 mRNA stability
AU - Inoue, Takeshi
AU - Morita, Masahiro
AU - Hijikata, Atsushi
AU - Yoko Fukuda-Yuzawa, Fukuda-Yuzawa
AU - Adachi, Shungo
AU - Isono, Kyoichi
AU - Ikawa, Tomokatsu
AU - Kawamoto, Hiroshi
AU - Koseki, Haruhiko
AU - Natsume, Tohru
AU - Fukao, Taro
AU - Ohara, Osamu
AU - Yamamoto, Tadashi
AU - Kurosaki, Tomohiro
N1 - Publisher Copyright:
© 2015 Inoue et al.
PY - 2015/8/24
Y1 - 2015/8/24
N2 - The CCR4-NOT deadenylase complex plays crucial roles in mRNA decay and translational repression induced by poly(A) tail shortening. Although the in vitro activities of each component of this complex have been well characterized, its in vivo role in immune cells remains unclear. Here we show that mice lacking the CNOT3 subunit of this complex, specifically in B cells, have a developmental block at the pro- to pre-B cell transition. CNOT3 regulated generation of germline transcripts in the VH region of the immunoglobulin heavy chain (Igh) locus, compaction of the locus, and subsequent Igh gene rearrangement and destabilized tumor suppressor p53 mRNA. The developmental defect in the absence of CNOT3 could be partially rescued by ablation of p53 or introduction of a prerearranged Igh transgene. Thus, our data suggest that the CCR4-NOT complex regulates B cell differentiation by controlling Igh rearrangement and destabilizing p53 mRNA.
AB - The CCR4-NOT deadenylase complex plays crucial roles in mRNA decay and translational repression induced by poly(A) tail shortening. Although the in vitro activities of each component of this complex have been well characterized, its in vivo role in immune cells remains unclear. Here we show that mice lacking the CNOT3 subunit of this complex, specifically in B cells, have a developmental block at the pro- to pre-B cell transition. CNOT3 regulated generation of germline transcripts in the VH region of the immunoglobulin heavy chain (Igh) locus, compaction of the locus, and subsequent Igh gene rearrangement and destabilized tumor suppressor p53 mRNA. The developmental defect in the absence of CNOT3 could be partially rescued by ablation of p53 or introduction of a prerearranged Igh transgene. Thus, our data suggest that the CCR4-NOT complex regulates B cell differentiation by controlling Igh rearrangement and destabilizing p53 mRNA.
UR - http://www.scopus.com/inward/record.url?scp=84961133809&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84961133809&partnerID=8YFLogxK
U2 - 10.1084/jem.20150384
DO - 10.1084/jem.20150384
M3 - Article
C2 - 26238124
AN - SCOPUS:84961133809
SN - 0022-1007
VL - 212
SP - 1465
EP - 1479
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 9
ER -