BACKGROUND: In phylogenetically diverse organisms, the 5' ends of a subset of mRNAs are trans-spliced with a spliced leader (SL) RNA. The functions of SL trans-splicing, however, remain largely enigmatic. RESULTS: We quantified translation genome-wide in the marine chordate, Oikopleura dioica, under inhibition of mTOR, a central growth regulator. Translation of trans-spliced TOP mRNAs was suppressed, consistent with a role of the SL sequence in nutrient-dependent translational control of growth-related mRNAs. Under crowded, nutrient-limiting conditions, O. dioica continued to filter-feed, but arrested growth until favorable conditions returned. Upon release from unfavorable conditions, initial recovery was independent of nutrient-responsive, trans-spliced genes, suggesting animal density sensing as a first trigger for resumption of development. CONCLUSION: Our results are consistent with a proposed role of trans-splicing in the coordinated translational down-regulation of nutrient-responsive genes under growth-limiting conditions.

Computational Biology Unit Department of Informatics University of Bergen Bergen Norway

Department of Biological Sciences University of Bergen Bergen Norway

Inst Expt Bot Czech Acad Sci Centre of the Region Hana for Biotechnological and Agricultural Research Olomouc Czech Republic

Sars International Centre for Marine Molecular Biology University of Bergen Bergen Norway

University of Ulm Ulm Germany

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Douris V, Telford MJ, Averof M. Evidence for multiple independent origins of trans-splicing in Metazoa. Mol Biol Evol. 2010;27:684–693. doi: 10.1093/molbev/msp286. PubMed DOI

Krchňáková Z, Krajčovič J, Vesteg M. On the possibility of an early evolutionary origin for the spliced leader trans-splicing. J Mol Evol. 2017;85:37–45. doi: 10.1007/s00239-017-9803-y. PubMed DOI

Hastings KE. SL trans-splicing: easy come or easy go? Trends Genet. 2005;21:240–247. doi: 10.1016/j.tig.2005.02.005. PubMed DOI

Blumenthal T, Gleason KS. Caenorhabditis elegans operons: form and function. Nat Rev Genet. 2003;4:110–118. doi: 10.1038/nrg995. PubMed DOI

Danks GB, Raasholm M, Campsteijn C, Long AM, Manak JR, Lenhard B, Thompson EM. Trans-splicing and operons in metazoans: translational control in maternally regulated development and recovery from growth arrest. Mol Biol Evol. 2015;32:585–599. doi: 10.1093/molbev/msu336. PubMed DOI

Danks G, Thompson EM. Trans-splicing in metazoans: a link to translational control? Worm. 2015;4:e1046030. doi: 10.1080/21624054.2015.1046030. PubMed DOI PMC

Levy S, Avni D, Hariharan N, Perry RP, Meyuhas O. Oligopyrimidine tract at the 5′ end of mammalian ribosomal protein mRNAs is required for their translational control. Proc Natl Acad Sci U S A. 1991;88:3319–3323. doi: 10.1073/pnas.88.8.3319. PubMed DOI PMC

Hsieh AC, Liu Y, Edlind MP, et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012;485:55–61. doi: 10.1038/nature10912. PubMed DOI PMC

Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature. 2012;485:109–113. doi: 10.1038/nature11083. PubMed DOI PMC

Zaslaver A, Baugh LR, Sternberg PW. Metazoan operons accelerate recovery from growth-arrested states. Cell. 2011;145:981–992. doi: 10.1016/j.cell.2011.05.013. PubMed DOI PMC

Troedsson C, Bouquet JM, Aksnes D, Thompson EM. Resource allocation between somatic growth and reproductive output in the pelagic chordate Oikopleura dioica allows opportunistic response to nutritional variation. Mar Ecol Prog Ser. 2002;243:83–91. doi: 10.3354/meps243083. DOI

Ganot P, Bouquet JM, Kallesøe T, Thompson EM. The Oikopleura coenocyst, a unique chordate germ cell permitting rapid, extensive modulation of oocyte production. Dev Biol. 2007;302:591–600. doi: 10.1016/j.ydbio.2006.10.021. PubMed DOI

Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem. 2009;284:8023–8032. doi: 10.1074/jbc.M900301200. PubMed DOI PMC

Subramaniam G, Campsteijn C, Thompson EM. Lifespan extension in a semelparous chordate occurs via developmental growth arrest just prior to meiotic entry. PLoS One. 2014;9:e93787. doi: 10.1371/journal.pone.0093787. PubMed DOI PMC

Ingolia NT, Brar GA, Rouskin S, McGeachy AM, Weissman JS. The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nat Protoc. 2012;7:1534–1550. doi: 10.1038/nprot.2012.086. PubMed DOI PMC

Ganot P, Kallesøe T, Thompson EM. The cytoskeleton organizes germ nuclei with divergent fates and asynchronous cycles in a common cytoplasm during oogenesis in the chordate Oikopleura. Dev Biol. 2007;302:577–590. doi: 10.1016/j.ydbio.2006.10.022. PubMed DOI

Ganot P, Moosmann-Schulmeister A, Thompson EM. Oocyte selection is concurrent with meiosis resumption in the coenocystic oogenesis of Oikopleura. Dev Biol. 2008;324:266–276. doi: 10.1016/j.ydbio.2008.09.016. PubMed DOI

Meyuhas O, Kahan T. The race to decipher the TOP secrets of TOP mRNAs. Biochim Biophys Acta. 2015;1849:801–811. doi: 10.1016/j.bbagrm.2014.08.015. PubMed DOI

Yokomori R, Shimai K, Nishitsuji K, Suzuki Y, Kusakabe TG, Nakai K. Genome-wide identification and characterization of transcription start sites and promoters in the tunicate Ciona intestinalis. Genome Res. 2016;26:140–150. doi: 10.1101/gr.184648.114. PubMed DOI PMC

Meyuhas O. Synthesis of the translational apparatus is regulated at the translational level. Eur J Biochem. 2001;267:6321–6330. doi: 10.1046/j.1432-1327.2000.01719.x. PubMed DOI

Ganot P, Kallesøe T, Reinhardt R, Chourrout D, Thompson EM. Spliced-leader RNA trans splicing in a chordate, Oikopleura dioica, with a compact genome. Mol Cell Biol. 2004;24:7795–7805. doi: 10.1128/MCB.24.17.7795-7805.2004. PubMed DOI PMC

Danks G, Campsteijn C, Parida M, et al. OikoBase: a genomics and developmental transcriptomics resource for the urochordate Oikopleura dioica. Nucleic Acids Res. 2013;41:D845–D853. doi: 10.1093/nar/gks1159. PubMed DOI PMC

Danks GB, Navratilova P, Lenhard B, Thompson EM. Distinct core promoter codes drive transcription initiation at key developmental transitions in a marine chordate. BMC Genomics. 2018;19:164. doi: 10.1186/s12864-018-4504-5. PubMed DOI PMC

Allen MA, Hillier LW, Waterston RH, Blumenthal T. A global analysis of C. elegans trans-splicing. Genome Res. 2011;21:255–264. doi: 10.1101/gr.113811.110. PubMed DOI PMC

Stadler M, Fire A. Conserved translatome remodeling in nematode species executing a shared developmental transition. PLoS Genet. 2013;9:e1003739. doi: 10.1371/journal.pgen.1003739. PubMed DOI PMC

Yang YF, Zhang X, Ma X, Zhao T, Sun Q, Huan Q, Wu S, Du Z, Qian W. Trans-splicing enhances translational efficiency in C. elegans. Genome Res. 2017;27:1525–1535. doi: 10.1101/gr.202150.115. PubMed DOI PMC

Avni D, Biberman Y, Meyuhas O. The 5′ terminal oligopyrimidine tract confers translational control on TOP mRNAs in a cell type- and sequence context-dependent manner. Nucleic Acids Res. 1997;25:995–1001. doi: 10.1093/nar/25.5.995. PubMed DOI PMC

Bouquet JM, Spriet E, Troedsson C, Otterå H, Chourrout D, Thompson EM. Culture optimization for the emergent zooplanktonic model organism Oikopleura dioica. J Plankton Res. 2009;31:359–370. doi: 10.1093/plankt/fbn132. PubMed DOI PMC

Sambrook J, Russell DW. Purification of nucleic acids by extraction with phenol:chloroform. 2006. PubMed

Olshen AB, Hsieh AC, Stumpf CR, Olshen RA, Ruggero D, Taylor BS. Assessing gene-level translational control from ribosome profiling. Bioinformatics. 2013;29:2995–3002. doi: 10.1093/bioinformatics/btt533. PubMed DOI PMC