Faculty of Health Sciences, University of Bristol, Bristol, UK.
Faculty of Life Sciences, University of Bristol, Bristol, UK.
Dev Dyn. 2023 Feb;252(2):276-293. doi: 10.1002/dvdy.537. Epub 2022 Sep 20.
Although splicing is an integral part of the expression of many genes in our body, genetic syndromes with spliceosomal defects affect only specific tissues. To help understand the mechanism, we investigated the expression pattern of a core protein of the major spliceosome, SmB/B' (Small Nuclear Ribonucleoprotein Polypeptides B/B'), which is encoded by SNRPB. Loss-of-function mutations of SNRPB in humans cause cerebro-costo-mandibular syndrome (CCMS) characterized by rib gaps, micrognathia, cleft palate, and scoliosis. Our expression analysis focused on the affected structures as well as non-affected tissues, using chick and mouse embryos as model animals.
Embryos at young stages (gastrula) showed ubiquitous expression of SmB/B'. However, the level and pattern of expression became tissue-specific as differentiation proceeded. The regions relating to CCMS phenotypes such as cartilages of ribs and vertebrae and palatal mesenchyme express SmB/B' in the nucleus sporadically. However, cartilages that are not affected in CCMS also showed similar expressions. Another spliceosomal gene, SNRNP200, which mutations cause retinitis pigmentosa, was also prominently expressed in cartilages in addition to the retina.
The expression of SmB/B' is spatiotemporally regulated during embryogenesis despite the ubiquitous requirement of the spliceosome, however, the expression pattern is not strictly correlated with the phenotype presentation.
尽管剪接是我们体内许多基因表达的一个组成部分,但具有剪接体缺陷的遗传综合征仅影响特定的组织。为了帮助理解这种机制,我们研究了主要剪接体核心蛋白 SmB/B'(小核核糖核蛋白多肽 B/B')的表达模式,SmB/B' 由 SNRPB 编码。人类 SNRPB 的功能丧失突变导致脑-面-颌骨综合征(CCMS),其特征为肋骨间隙、小颌畸形、腭裂和脊柱侧凸。我们的表达分析集中在受影响的结构以及非受影响的组织上,使用鸡和小鼠胚胎作为模型动物。
在早期(原肠胚)胚胎中,SmB/B' 呈现广泛表达。然而,随着分化的进行,表达水平和模式变得具有组织特异性。与 CCMS 表型相关的区域,如肋骨和脊椎骨的软骨和腭间充质,偶尔在细胞核中表达 SmB/B'。然而,CCMS 不受影响的软骨也表现出类似的表达。另一个剪接体基因 SNRNP200,其突变导致视网膜色素变性,除了视网膜外,在软骨中也有明显表达。
尽管剪接体普遍需要,但 SmB/B' 的表达在胚胎发生过程中是时空调节的,然而,表达模式与表型表现并不严格相关。