Identification of CR43467 encoding a long non-coding RNA as a novel genetic interactant with dFIG4, a CMT-causing gene.
Identification of CR43467 encoding a long non-coding RNA as a novel genetic interactant with dFIG4, a CMT-causing gene.
复制标题
鉴定编码长非编码 RNA 的 CR43467 作为与 dFIG4（一种 CMT 致病基因）的新型遗传相互作用物。
DOI：
10.1016/j.yexcr.2019.111711
复制
发表时间：
2020
影响因子：
3.7
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Shimada;S.; Muraoka;Y.; Ibaraki;K.; Takano-Shimizu-Kouno;T.; Yoshida;H.;and Yamaguchi;M.
DFIG4是果蝇中FIG4的同源物，是夏科特-玛丽-图斯病(CMT)的致病基因之一，它的眼睛想象盘特异性敲除dFIG4，导致成人复眼形态异常，即所谓的粗糙眼表型。我们先前对dFIG4基因敲除诱导的粗糙眼表型进行了修饰筛选，并发现包括CR18854在内的几个基因编码一个长的非编码RNA(LncRNA)，作为与dFIG4的遗传交互作用。在本研究中，我们在更广泛的遗传筛选中发现，同时编码气味感受器46a(Or46a)和lncRNA CR43467的基因座的缺失有效地抑制了dFIG4基因敲除引起的粗眼表型。这两个基因位于相同的基因座上，但方向相反。为了确定这些基因中哪些负责抑制粗眼表型，我们使用CRISPR-dCas9系统建立了CR43467特异的基因敲除系。利用这个系统，我们证明了CR43467基因，而不是O46agene基因，与dFIG4基因存在遗传上的相互作用。CR43467基因的敲除挽救了由FIG4基因敲除引起的神经肌肉接头处突触分支长度和突触数的减少。CR43467基因的敲除也有效地抑制了脂肪体特异性FIG4基因敲除引起的空泡增大表型。CR43467基因的敲除也抑制了其他周围神经病相关基因如COA7、dHADHB和PDHB诱导的粗糙眼表型。在此，我们鉴定了另一个编码lncRNA的基因CR43467，它与引起CMT的基因存在遗传交互作用。
The eye imaginal disc-specific knockdown ofdFIG4, aDrosophilahomolog ofFIG4that is one of the Charcot-Marie-Tooth disease (CMT)-causing genes, induces an aberrant adult compound eye morphology, the so-called rough eye phenotype. We previously performed modifier screening on thedFIG4knockdown-induced rough eye phenotype and identified several genes, includingCR18854, encoding a long non-coding RNA (lncRNA) as genetic interactants withdFIG4. In the present study, in more extensive genetic screening, we found that the deletion of a gene locus encoding both Odorant rector 46a (Or46a) and lncRNA CR43467 effectively suppressed the rough eye phenotype induced by the knockdown ofdFIG4. Both genes were located on the same locus, but oriented in opposite directions. In order to identify which of these genes is responsible for the suppression of the rough eye phenotype, we established aCR43467-specific knockdown line using the CRISPR-dCas9 system. By using this system, we demonstrated that theCR43467gene, but not theOr46agene, genetically interacted with thedFIG4gene. The knockdown ofCR43467rescued the reductions in the length of synaptic branches and number of boutons at neuromuscular junctions induced by the knockdown ofdFIG4. The vacuole enlargement phenotype induced by the fat body-specificdFIG4knockdown was also effectively suppressed by the knockdown ofCR43467. The knockdown ofCR43467also suppressed the rough eye phenotype induced by other peripheral neuropathy-related genes, such asdCOA7,dHADHB, anddPDHB. We herein identified another gene encoding lncRNA,CR43467as a genetic interactant with the CMT-causing gene.
登录
查看更多内容
影响因子：
9.8
作者：
Campeau, Philippe M.;Lenk, Guy M.;Lee, Brendan H.
通讯作者：
Lee, Brendan H.
影响因子：
9.8
作者：
Chow, Clement Y.;Landers, John E.;Meisler, Miriam H.
通讯作者：
Meisler, Miriam H.
人丙酮酸脱氢酶复合物缺乏症的临床和生化谱
影响因子：
5.2
作者：
G. Brown;R. M. Brown;R. Scholem;D. Kirby;H. Dahl
通讯作者：
H. Dahl
日本腓骨肌萎缩症的分子诊断和临床发病评论
影响因子：
3.5
作者：
Ichihara G;et al;五ノ井透;Itsuo Chiba et al.;Nakagawa M
通讯作者：
Nakagawa M
DOI：
10.1006/bbrc.1994.1302
发表时间：
1994-03-15
影响因子：
3.1
作者：
KAMIJO, T;AOYAMA, T;HASHIMOTO, T
通讯作者：
HASHIMOTO, T