The complex, dynamic SpliceOme of the small GTPase transcripts altered by technique, sex, genetics, tissue specificity, and RNA base editing.
The complex, dynamic SpliceOme of the small GTPase transcripts altered by technique, sex, genetics, tissue specificity, and RNA base editing.
复制标题
DOI：
10.3389/fcell.2022.1033695
复制
发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
小的GTdR家族在癌症和细胞生理学中被充分研究。有162个注释的人类基因，该家族在整个身体细胞中广泛表达。该家族的成员具有需要剪接的多个外显子。然而，剪接在家庭中的作用还没有得到充分的探索。我们通过整合Nanopore和Illumina测序技术研究了41，671个样本中小GTP酶的剪接动力学。在这项工作中，我们有了一些发现。1）。使用92个样本的GTEx长读段数据，每个小GTdR基因平均有两个转录本，其中83个基因（51%）表达两种或更多种亚型。2）。来自17，382个样本的GTEx的跨组织分析显示，41个基因（25%）表达两种或更多种蛋白质编码亚型。这些包括RHOA、RAB 37、RAB 40 C、RAB 4 B、RAB 5C、RHOC、RAB 1A、RAN、RHEB、RAC 1和KRAS等基因中的蛋白质改变转录物。3）。RNAseq的分离和文库技术影响了小GTP酶的无义介导的衰变和保留内含子转录物的丰度，这在基因中观察到的频率比预期的要高。4）。对16，243个“血液PAXgene”样本的分析鉴定出7个基因（3.7%; RHOA，RAB 40 C，RAB 4 B，RAB 37，RAB 5 B，RAB 5C，RHOC），其中两个或更多个转录本表达为主要同种型（占总基因的75%），表明遗传学在改变剪接中的作用。5）。罕见（ARL 6、RAB 23、ARL 13 B、HRAS、NRAS）和常见变异（GEM、RHOC、MRAS、RAB 5 B、RERG、ARL 16）可影响剪接并对表型和疾病产生影响。6）。多个基因（RAB 9A、RAP 2C、ARL 4A、RAB 3A、RAB 26、RAB 3C、RASL 10A、RAB 40 B和HRAS）在转录表达方面具有性别差异。7）。在一种或多种形式的癌症中，包括或排除了小GT3基因（RASEF、KRAS、RAC 1、RHEB、ARL 4A、RHOA、RAB 30、RHOBTB 1、ARL 16、RAP 1A）的几个外显子。8）。10个转录本（SAR 1B、IFFT 27、ARL 14、RAB 11 A、RAB 10、RAB 38、RAN、RIT 1、RAB 9A）在缺氧条件下发生了改变，其中RHOA在其所有转录本的保守位点上都有短暂的3′UTR RNA碱基编辑。总的来说，我们展示了一个显着的和动态的作用，拼接内的小GTALGOT家庭，需要未来的探索。
The small GTPase family is well-studied in cancer and cellular physiology. With 162 annotated human genes, the family has a broad expression throughout cells of the body. Members of the family have multiple exons that require splicing. Yet, the role of splicing within the family has been underexplored. We have studied the splicing dynamics of small GTPases throughout 41,671 samples by integrating Nanopore and Illumina sequencing techniques. Within this work, we have made several discoveries. 1). Using the GTEx long read data of 92 samples, each small GTPase gene averages two transcripts, with 83 genes (51%) expressing two or more isoforms. 2). Cross-tissue analysis of GTEx from 17,382 samples shows 41 genes (25%) expressing two or more protein-coding isoforms. These include protein-changing transcripts in genes such as RHOA, RAB37, RAB40C, RAB4B, RAB5C, RHOC, RAB1A, RAN, RHEB, RAC1, and KRAS. 3). The isolation and library technique of the RNAseq influences the abundance of non-sense-mediated decay and retained intron transcripts of small GTPases, which are observed more often in genes than appreciated. 4). Analysis of 16,243 samples of “Blood PAXgene” identified seven genes (3.7%; RHOA, RAB40C, RAB4B, RAB37, RAB5B, RAB5C, RHOC) with two or more transcripts expressed as the major isoform (75% of the total gene), suggesting a role of genetics in altering splicing. 5). Rare (ARL6, RAB23, ARL13B, HRAS, NRAS) and common variants (GEM, RHOC, MRAS, RAB5B, RERG, ARL16) can influence splicing and have an impact on phenotypes and diseases. 6). Multiple genes (RAB9A, RAP2C, ARL4A, RAB3A, RAB26, RAB3C, RASL10A, RAB40B, and HRAS) have sex differences in transcript expression. 7). Several exons are included or excluded for small GTPase genes (RASEF, KRAS, RAC1, RHEB, ARL4A, RHOA, RAB30, RHOBTB1, ARL16, RAP1A) in one or more forms of cancer. 8). Ten transcripts are altered in hypoxia (SAR1B, IFT27, ARL14, RAB11A, RAB10, RAB38, RAN, RIT1, RAB9A) with RHOA identified to have a transient 3′UTR RNA base editing at a conserved site found in all of its transcripts. Overall, we show a remarkable and dynamic role of splicing within the small GTPase family that requires future explorations.