Skip to main content
Log in

A repertoire of intronic lariat RNAs reveals tissue-specific regulation and target mimicry potential in plants

  • Research Paper
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

Lariat RNA is concomitantly produced by excised intron during RNA splicing, which is usually debranched by DBR1, an RNA debranching enzyme. However, increasing evidence showed that some lariat RNA could escape debranching. Little is known about how and why these lariat RNAs could be retained. By comparing the atlas of lariat RNAs between the non-dividing cell (mature pollen) and three actively dividing tissues (young shoot apex, young seeds, and young roots), we identified hundreds to thousands of lariat RNA naturally retained in each tissue, and the incidence of lariat RNA retention is much less in shoot apex while much more in pollen. Many lariat RNAs derived from the same intron or different lariat RNAs from the same pre-mRNA could be retained in one tissue while degraded in the other tissues. By deciphering lariat RNA sequences, we identified an AG-rich (RAAAAVAAAR) motif and a UC-rich (UCUCUYUCUC) motif for pollen-specific and the other three tissues-retained lariat RNAs, respectively. Reconstitution of the pollen-specific AG-rich motif indeed enhanced lariat RNA retention in plants. Biologically, hundreds of lariat RNAs harbored miRNA binding sites, and dual-luciferase reporter assay showed that these natural lariat RNAs had the potential to protect expression of miRNA target genes. Collectively, our results uncover that selective retention of lariat RNA is an actively regulatory process, and provide new insights into understanding how lariat RNA metabolism may impact miRNA activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bailey, T.L., Johnson, J., Grant, C.E., and Noble, W.S. (2015). The MEME suite. Nucleic Acids Res 43, W39–W49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bitton, D.A., Rallis, C., Jeffares, D.C., Smith, G.C., Chen, Y.Y.C., Codlin, S., Marguerat, S., and Bähler, J. (2014). LaSSO, a strategy for genome-wide mapping of intronic lariats and branch points using RNA-seq. Genome Res 24, 1169–1179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chapman, K.B., and Boeke, J.D. (1991). Isolation and characterization of the gene encoding yeast debranching enzyme. Cell 65, 483–492.

    Article  CAS  PubMed  Google Scholar 

  • Chen, S., Zhou, Y., Chen, Y., and Gu, J. (2018). fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34, i884–i890.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheng, J., Zhang, Y., Li, Z., Wang, T., Zhang, X., and Zheng, B. (2018). A lariat-derived circular RNA is required for plant development in Arabidopsis. Sci China Life Sci 61, 204–213.

    Article  CAS  PubMed  Google Scholar 

  • Choi, Y., Lee, H.H., Park, J., Kim, S., Choi, S., Moon, H., Shin, J., Kim, J.E., Choi, G.J., Seo, Y.S., et al. (2022). Intron turnover is essential to the development and pathogenicity of the plant pathogenic fungus Fusarium graminearum. Commun Biol 5, 1129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai, X., Zhuang, Z., and Zhao, P.X. (2018). psRNATarget: a plant small RNA target analysis server (2017 release). Nucleic Acids Res 46, W49–W54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grant, C.E., Bailey, T.L., and Noble, W.S. (2011). FIMO: scanning for occurrences of a given motif. Bioinformatics 27, 1017–1018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grishok, A., Pasquinelli, A.E., Conte, D., Li, N., Parrish, S., Ha, I., Baillie, D.L., Fire, A., Ruvkun, G., and Mello, C.C. (2001). Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106, 23–34.

    Article  CAS  PubMed  Google Scholar 

  • Hansen, T.B., Jensen, T.I., Clausen, B.H., Bramsen, J.B., Finsen, B., Damgaard, C.K., and Kjems, J. (2013). Natural RNA circles function as efficient microRNA sponges. Nature 495, 384–388.

    Article  CAS  PubMed  ADS  Google Scholar 

  • Kim, D., Paggi, J.M., Park, C., Bennett, C., and Salzberg, S.L. (2019). Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol 37, 907–915.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, H.C., Kim, G.M., Yang, J.M., and Ki, J.W. (2001). Cloning, expression, and complementation test of the RNA lariat debranching enzyme cDNA from mouse. Mol Cells 11, 198–203.

    Article  CAS  PubMed  Google Scholar 

  • Kim, J.W., Kim, H.C., Kim, G.M., Yang, J.M., Boeke, J.D., and Nam, K. (2000). Human RNA lariat debranching enzyme cDNA complements the phenotypes of Saccharomyces cerevisiae dbr1 and Schizosaccharomyces pombe dbr1 mutants. Nucleic Acids Res 28, 3666–3673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kozomara, A., Birgaoanu, M., and Griffiths-Jones, S. (2019). miRBase: from microRNA sequences to function. Nucleic Acids Res 47, D155–D162.

    Article  CAS  PubMed  Google Scholar 

  • Lawrence, M., Huber, W., Pages, H., Aboyoun, P., Carlson, M., Gentleman, R., Morgan, M.T., and Carey, V.J. (2013). Software for computing and annotating genomic ranges. PLoS Comput Biol 9, e1003118.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., and Durbin, R. (2009). The sequence alignment/map format and SAMtools. Bioinformatics 25, 2078–2079.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li, Z., Wang, S., Cheng, J., Su, C., Zhong, S., Liu, Q., Fang, Y., Yu, Y., Lv, H., Zheng, Y., et al. (2016). Intron lariat RNA inhibits microRNA biogenesis by sequestering the dicing complex in Arabidopsis. PLoS Genet 12, e1006422.

    Article  PubMed  PubMed Central  Google Scholar 

  • Liao, Y., Smyth, G.K., and Shi, W. (2013). The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res 41, e108.

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu, L., Lu, Y., Wei, L., Yu, H., Cao, Y., Li, Y., Yang, N., Song, Y., Liang, C., and Wang, T. (2018). Transcriptomics analyses reveal the molecular roadmap and long non-coding RNA landscape of sperm cell lineage development. Plant J 96, 421–437.

    Article  CAS  PubMed  Google Scholar 

  • Liu, Q., Wang, F., and Axtell, M.J. (2014). Analysis of complementarity requirements for plant MicroRNA targeting using a Nicotiana benthamiana quantitative transient assay. Plant Cell 26, 741–753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550.

    Article  PubMed  PubMed Central  Google Scholar 

  • Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S.D., Gregersen, L.H., Munschauer, M., et al. (2013). Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495, 333–338.

    Article  CAS  PubMed  ADS  Google Scholar 

  • Mercer, T.R., Clark, M.B., Andersen, S.B., Brunck, M.E., Haerty, W., Crawford, J., Taft, R.J., Nielsen, L.K., Dinger, M.E., and Mattick, J.S. (2015). Genome-wide discovery of human splicing branchpoints. Genome Res 25, 290–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nam, K, Lee, G., Trambley, J., Devine, S.E., and Boeke, J.D. (1997). Severe growth defect in a Schizosaccharomyces pombe mutant defective in intron lariat degradation. Mol Cell Biol 17, 809–818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oliver, C., Annacondia, M.L., Wang, Z., Jullien, P.E., Slotkin, R.K., Köhler, C., and Martinez, G. (2022). The miRNome function transitions from regulating developmental genes to transposable elements during pollen maturation. Plant Cell 34, 784–801.

    Article  PubMed  Google Scholar 

  • Park, W., Li, J., Song, R., Messing, J., and Chen, X. (2002). CARPEL FACTORY, a dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana. Curr Biol 12, 1484–1495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pertea, M., Pertea, G.M., Antonescu, C.M., Chang, T.C., Mendell, J.T., and Salzberg, S. L. (2015). StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat Biotechnol 33, 290–295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quinlan, A.R., and Hall, I.M. (2010). BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramírez, F., Dündar, F., Diehl, S., Grüning, B.A., and Manke, T. (2014). deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res 42, W187–W191.

    Article  PubMed  PubMed Central  Google Scholar 

  • Robinson, M.D., McCarthy, D.J., and Smyth, G.K. (2010). edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140.

    Article  CAS  PubMed  Google Scholar 

  • Ruskin, B., Krainer, A.R., Maniatis, T., and Green, M.R. (1984). Excision of an intact intron as a novel lariat structure during pre-mRNA splicing in vitro. Cell 38, 317–331.

    Article  CAS  PubMed  Google Scholar 

  • Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012). Fiji: an open-source platform for biological-image analysis. Nat Methods 9, 676–682.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki, H., Zuo, Y., Wang, J., Zhang, M.Q., Malhotra, A., and Mayeda, A. (2006). Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing. Nucleic Acids Res 34, e63.

    Article  PubMed  PubMed Central  Google Scholar 

  • Taggart, A.J., DeSimone, A.M., Shih, J.S., Filloux, M.E., and Fairbrother, W.G. (2012). Large-scale mapping of branchpoints in human pre-mRNA transcripts in vivo. Nat Struct Mol Biol 19, 719–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taggart, A.J., Lin, C.L., Shrestha, B., Heintzelman, C., Kim, S., and Fairbrother, W.G. (2017). Large-scale analysis of branchpoint usage across species and cell lines. Genome Res 27, 639–649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talhouarne, G.J.S., and Gall, J.G. (2014). Lariat intronic RNAs in the cytoplasm of Xenopus tropicalis oocytes. RNA 20, 1476–1487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talhouarne, G.J.S., and Gall, J.G. (2018). Lariat intronic RNAs in the cytoplasm of vertebrate cells. Proc Natl Acad Sci USA 115, E7970–E7977.

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  • Tay, M.L.I., and Pek, J.W. (2017). Maternally inherited stable intronic sequence RNA triggers a self-reinforcing feedback loop during development. Curr Biol 27, 1062–1067.

    Article  CAS  PubMed  Google Scholar 

  • Thorvaldsdottir, H., Robinson, J.T., and Mesirov, J.P. (2013). Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinf 14, 178–192.

    Article  CAS  Google Scholar 

  • Varkonyi-Gasic, E., Wu, R., Wood, M., Walton, E.F., and Hellens, R.P. (2007). Protocol: a highly sensitive RT-PCR method for detection and quantification of microRNAs. Plant Methods 3, 12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang, H., Hill, K., and Perry, S.E. (2004). An Arabidopsis RNA lariat debranching enzyme is essential for embryogenesis. J Biol Chem 279, 1468–1473.

    Article  CAS  PubMed  Google Scholar 

  • Wang, T., Zhang, X., and Zheng, B. (2021). Identification of intronic lariat-derived circular RNAs in Arabidopsis by RNA deep sequencing. In: Vaschetto, L.M., ed. Plant Circular RNAs. Methods in Molecular Biology. New York: Humana. 93–100.

    Chapter  Google Scholar 

  • Wu, W., Li, L., Zhao, Y., Zhao, Y., Jiang, T., McCormick, S., and Zheng, B. (2021). Heterochromatic silencing is reinforced by ARID1-mediated small RNA movement in Arabidopsis pollen. New Phytol 229, 3269–3280.

    Article  CAS  PubMed  Google Scholar 

  • Yu, Y., Zhang, H., Long, Y., Shu, Y., and Zhai, J. (2022). Plant Public RNA-seq Database: a comprehensive online database for expression analysis of ∼45 000 plant public RNA-Seq libraries. Plant Biotechnol J 20, 806–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, S.Y., Clark, N.E., Freije, C.A., Pauwels, E., Taggart, A.J., Okada, S., Mandel, H., Garcia, P., Ciancanelli, M.J., Biran, A., et al. (2018). Inborn errors of RNA lariat metabolism in humans with brainstem viral infection. Cell 172, 952–965.e18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, X., Zhang, Y., Wang, T., Li, Z., Cheng, J., Ge, H., Tang, Q., Chen, K., Liu, L., Lu, C., et al. (2019). A comprehensive map of intron branchpoints and lariat RNAs in plants. Plant Cell 31, 956–973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y., Zhang, X.O., Chen, T., Xiang, J.F., Yin, Q.F., Xing, Y.H., Zhu, S., Yang, L., and Chen, L.L. (2013). Circular intronic long noncoding RNAs. Mol Cell 51, 792–806.

    Article  CAS  PubMed  Google Scholar 

  • Zheng, S., Vuong, B.Q., Vaidyanathan, B., Lin, J.Y., Huang, F.T., and Chaudhuri, J. (2015). Non-coding RNA generated following lariat debranching mediates targeting of AID to DNA. Cell 161, 762–773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgement

This work was supported by the National Natural Science Foundation of China (31830045, 32025005, 32100429). We are grateful to Dr. Yiliang Ding for critical reading of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Binglian Zheng.

Ethics declarations

The author(s) declare that they have no conflict of interest.

Supporting Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Zhang, X., Tang, Q. et al. A repertoire of intronic lariat RNAs reveals tissue-specific regulation and target mimicry potential in plants. Sci. China Life Sci. (2024). https://doi.org/10.1007/s11427-023-2466-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11427-023-2466-7

Navigation