RT Journal
A1 Yang, Yu-Fei
A1 Zhang, Xiaoqing
A1 Ma, Xuehua
A1 Zhao, Taolan
A1 Sun, Qiushi
A1 Huan, Qing
A1 Wu, Shaohuan
A1 Du, Zhuo
A1 Qian, Wenfeng
T1 Trans-splicing enhances translational efficiency in C. elegans
JF Genome Research 
JO Genome Research 
YR 2017 
FD September 01 
VO 27 
IS 9 
SP 1525 
OP 1535 
DO 10.1101/gr.202150.115 
UL http://genome.cshlp.org/content/27/9/1525.abstract 
AB Translational efficiency is subject to extensive regulation. However, the factors influencing such regulation are poorly understood. In Caenorhabditis elegans, 62% of genes are trans-spliced to a specific spliced leader (SL1), which replaces part of the native 5′ untranslated region (5′ UTR). Given the pivotal role the 5′ UTR plays in the regulation of translational efficiency, we hypothesized that SL1 trans-splicing functions to regulate translational efficiency. With genome-wide analysis on Ribo-seq data, polysome profiling experiments, and CRISPR-Cas9–based genetic manipulation of trans-splicing sites, we found four lines of evidence in support of this hypothesis. First, SL1 trans-spliced genes have higher translational efficiencies than non-trans-spliced genes. Second, SL1 trans-spliced genes have higher translational efficiencies than non-trans-spliced orthologous genes in other nematode species. Third, an SL1 trans-spliced isoform has higher translational efficiency than the non-trans-spliced isoform of the same gene. Fourth, deletion of trans-splicing sites of endogenous genes leads to reduced translational efficiency. Importantly, we demonstrated that SL1 trans-splicing plays a key role in enhancing translational efficiencies of essential genes. We further discovered that SL1 trans-splicing likely enhances translational efficiency by shortening the native 5′ UTRs, hence reducing the presence of upstream start codons (uAUG) and weakening mRNA secondary structures. Taken together, our study elucidates the global function of trans-splicing in enhancing translational efficiency in nematodes, paving the way for further understanding the genomic mechanisms of translational regulation.