Alternative splicing and retinal degeneration.
Alternative splicing and retinal degeneration.
复制标题
DOI：
10.1111/cge.12181
复制
发表时间：
2013-08
影响因子：
3.5
通讯作者：
Zack DJ
中科院分区：
文献类型：
--
作者：
Liu MM;Zack DJ
选择性剪接在组织特异性和发育特异性模式中受到高度调控，据估计，15%的致病点突变影响前mRNA剪接。在这篇综述中，我们考虑了顺式作用的剪接位点和反式作用的剪接因子突变，它们影响前mRNA的剪接并导致视网膜变性。在视网膜色素变性和各种视锥视杆细胞营养不良中已经发现了大量的剪接点突变。例如，广泛表达的RPGR和COL2A1基因的视网膜特异外显子的选择性剪接突变分别主要导致X连锁视网膜色素变性和眼部Stickler综合征的变异。此外，常见的前mRNA剪接因子突变，如PRPF31、PRPF8和PRPF3，主要导致常染色体显性遗传性视网膜色素变性。这些发现表明，Pre-mRNA剪接在视网膜内稳态和视网膜退行性疾病的发病机制中起着重要作用。调控异常剪接的新治疗策略的发展，包括基于小分子的治疗，有可能导致视网膜退行性疾病的新治疗方法的发展。
Alternative splicing is highly regulated in tissue-specific and development-specific patterns, and it has been estimated that 15% of disease-causing point mutations affect pre-mRNA splicing. In this review, we consider the cis-acting splice site and trans-acting splicing factor mutations that affect pre-mRNA splicing and contribute to retinal degeneration. Numerous splice site mutations have been identified in retinitis pigmentosa and various cone-rod dystrophies. For example, mutations in alternatively spliced retina-specific exons of the widely expressed RPGR and COL2A1 genes lead primarily to X-linked retinitis pigmentosa and ocular variants of Stickler Syndrome, respectively. Furthermore, mutations in general pre-mRNA splicing factors, such as PRPF31, PRPF8, and PRPF3, predominantly cause autosomal dominant retinitis pigmentosa. These findings suggest an important role for pre-mRNA splicing in retinal homeostasis and the pathogenesis of retinal degenerative diseases. The development of novel therapeutic strategies to modulate aberrant splicing, including small molecule based therapies, has the potential to lead to the development of new treatments for retinal degenerative diseases.
登录
查看更多内容
影响因子：
--
作者：
Audo I;Bujakowska K;Mohand-Saïd S;Lancelot ME;Moskova-Doumanova V;Waseem NH;Antonio A;Sahel JA;Bhattacharya SS;Zeitz C
通讯作者：
Zeitz C
影响因子：
4.4
作者：
Graziotto, John J.;Farkas, Michael H.;Pierce, Eric A.
通讯作者：
Pierce, Eric A.
影响因子：
3.5
作者：
Comitato, Antonella;Spampanato, Carmine;Marigo, Valeria
通讯作者：
Marigo, Valeria
影响因子：
3.5
作者：
Hartmann, AM;Rujescu, D;Stamm, S
通讯作者：
Stamm, S
影响因子：
9.8
作者：
Fujita, R;Buraczynska, M;Swaroop, A
通讯作者：
Swaroop, A