Computational Biology and Bioinformatics

| Peer-Reviewed |

The Importance of Stiff Change of U(T) Content Around Splicing Sites in Efficient Plant Intron Splicing -- A Case Study in Rice

Received: 20 April 2023    Accepted: 12 May 2023    Published: 5 June 2023
Views:       Downloads:

Share This Article

Abstract

Pre-mRNAs splicing is one of the fundamental process which generates multiple transcripts from a single gene, contributing to transcriptome and proteome diversity. AS is regulated by the cooperation of trans-factors and cis-elements. In plants, extensive alternative splicing occurs not only in tissue-specific manner but also in response to stress conditions. Intron retention is the most predominant splicing type. However, the cis-elements regulating intron retention are still ambiguous in plants, especially under environmental stresses. This study aimed to elucidate the cis-elements underlying intron retention in plants under adverse enrironments. Using RNA-seq data of rice cultivars IRAT109 and ZS97 under drought environments, we compared the sequence characteristics between constitutive and retained introns. The results show that the main AS types include intron retention (IR), alternative acceptor sites (AA), alternative donor sites (AD) and cassette exon (exon skipping, ES). Among of them, IR was the prevelent pattern with frequencies of 30.8-31.2%. Motif analysis of 5' and 3' 200bp intron sequences found rich U(T) in the motifs for both constitutive and retained introns. By further analysis of base composition of sequences flanking splice sites, we detected a notable difference in U(T) content between introns and their neighboring exons in constitutive introns, but not in retained introns. The results in this study suggested that the lack of significant changes in U(T) content between retained introns and neighboring exons might be a potential cis feature of intron retention.

DOI 10.11648/j.cbb.20231101.12
Published in Computational Biology and Bioinformatics (Volume 11, Issue 1, June 2023)
Page(s) 13-18
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Alternative Splicing, Intron Retention, Cis-elements, Rice, Drought Stress

References
[1] Amit M, Donyo M, Hollander D, Goren A, Kim E, Gelfman S, Lev-Maor G, Burstein D, Schwartz S, Postolsky B, Pupko T, Ast G (2012) Differential GC content between exons and introns establishes distinct strategies of splice-site recognition. Cell Rep 1: 543-556.
[2] Apostolidi M, Stamatopoulou V (2023) Aberrant splicing in human cancer: An RNA structural code point of view. Front Pharmacol 14: 1137154.
[3] Bao S, Moakley DF, Zhang C (2019) The Splicing Code Goes Deep. Cell 176: 414-416.
[4] Baralle F, Giudice J (2017) Alternative splicing as a regulator of development and tissue identity. Nat Rev Mol Cell Biol 18: 437-451.
[5] Baralle M, Baralle FE (2018) The splicing code. Biosystems 164: 39-48.
[6] Bou Sleiman M, Frochaux MV, Andreani T, Osman D, Guigo R, Deplancke B (2020) Enteric infection induces Lark-mediated intron retention at the 5' end of Drosophila genes. Genome Biol 21: 4.
[7] Braunschweig U, Barbosa-Morais NL, Pan Q, Nachman EN, Alipanahi B, Gonatopoulos-Pournatzis T, Frey B, Irimia M, Blencowe BJ (2014) Widespread intron retention in mammals functionally tunes transcriptomes. Genome Res 24: 1774-1786.
[8] Chang CY, Lin WD, Tu SL (2014) Genome-Wide Analysis of Heat-Sensitive Alternative Splicing in Physcomitrella patens. Plant Physiol 165: 826-840.
[9] Foissac S, Sammeth M (2007) ASTALAVISTA: dynamic and flexible analysis of alternative splicing events in custom gene datasets. Nucleic Acids Res 35: W297-299.
[10] Ghosh S, Chan CK (2016) Analysis of RNA-Seq Data Using TopHat and Cufflinks. Methods Mol Biol 1374: 339-361.
[11] Goodall GJ, Filipowicz W (1989) The AU-rich sequences present in the introns of plant nuclear pre-mRNAs are required for splicing. Cell 58: 473-483.
[12] Hia F, Yang SF, Shichino Y, Yoshinaga M, Murakawa Y, Vandenbon A, Fukao A, Fujiwara T, Landthaler M, Natsume T, Adachi S, Iwasaki S, Takeuchi O (2019) Codon bias confers stability to human mRNAs. EMBO Rep 20: e48220.
[13] Jacob AG, Smith CWJ (2017) Intron retention as a component of regulated gene expression programs. Hum Genet 136: 1043-1057.
[14] Lemaire S, Fontrodona N, Aube F, Claude JB, Polveche H, Modolo L, Bourgeois CF, Mortreux F, Auboeuf D (2019) Characterizing the interplay between gene nucleotide composition bias and splicing. Genome Biol 20: 259.
[15] Liu J, Zhang Y, Zheng Y, Zhu Y, Shi Y, Guan Z, Lang K, Shen D, Huang W, Dou D (2023) PlantExp: a platform for exploration of gene expression and alternative splicing based on public plant RNA-seq samples. Nucleic Acids Res 51: D1483-D1491.
[16] Lorkovic ZJ, Wieczorek Kirk DA, Lambermon MH, Filipowicz W (2000) Pre-mRNA splicing in higher plants. Trends Plant Sci 5: 160-167.
[17] Louadi Z, Oubounyt M, Tayara H, Chong KT (2019) Deep Splicing Code: Classifying Alternative Splicing Events Using Deep Learning. Genes (Basel) 10.
[18] Marquez Y, Brown JW, Simpson C, Barta A, Kalyna M (2012) Transcriptome survey reveals increased complexity of the alternative splicing landscape in Arabidopsis. Genome Res 22: 1184-1195.
[19] Muhammad S, Xu X, Zhou W, Wu L (2022) Alternative splicing: An efficient regulatory approach towards plant developmental plasticity. Wiley Interdiscip Rev RNA: e1758.
[20] Neitz M, Neitz J (2021) Intermixing the OPN1LW and OPN1MW Genes Disrupts the Exonic Splicing Code Causing an Array of Vision Disorders. Genes (Basel) 12.
[21] Nystrom SL, McKay DJ (2021) Memes: A motif analysis environment in R using tools from the MEME Suite. PLoS Comput Biol 17: e1008991.
[22] Reddy A, Maria K, Barta A (2013) Complexity of the alternative splicing landscape in plants. Plant Cell 25: 3657-3683.
[23] Reddy AS, Rogers MF, Richardson DN, Hamilton M, Ben-Hur A (2012) Deciphering the plant splicing code: experimental and computational approaches for predicting alternative splicing and splicing regulatory elements. Front Plant Sci 3: 18.
[24] Rogalska ME, Vivori C, Valcarcel J (2023) Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects. Nat Rev Genet 24: 251-269.
[25] Rong S, Buerer L, Rhine CL, Wang J, Cygan KJ, Fairbrother WG (2020) Mutational bias and the protein code shape the evolution of splicing enhancers. Nat Commun 11: 2845.
[26] Sanchez SE, Petrillo E, Kornblihtt AR, Yanovsky MJ (2011) Alternative splicing at the right time. RNA Biol 8: 954-959.
[27] Smith LD, Lucas CM, Eperon IC (2013) Intron retention in the alternatively spliced region of RON results from weak 3' splice site recognition. PLoS One 8: e77208.
[28] Syed NH, Kalyna M, Marquez Y, Barta A, Brown JW (2012) Alternative splicing in plants--coming of age. Trends Plant Sci 17: 616-623.
[29] Thatcher SR, Zhou W, Leonard A, Wang BB, Beatty M, Zastrow-Hayes G, Zhao X, Baumgarten A, Li B (2014) Genome-wide analysis of alternative splicing in Zea mays: landscape and genetic regulation. Plant Cell 26: 3472-3487.
[30] Trapnell C, Pachter L, Salzberg SL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25: 1105-1111.
[31] Xing Y, Wang Q, Lee C (2006) Evolutionary divergence of exon flanks: a dissection of mutability and selection. Genetics 173: 1787-1791.
[32] Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RK, Hua Y, Gueroussov S, Najafabadi HS, Hughes TR, Morris Q, Barash Y, Krainer AR, Jojic N, Scherer SW, Blencowe BJ, Frey BJ (2015) RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Science 347: 1254806.
[33] Xue R, Mo R, Cui D, Cheng W, Wang H, Qin J, Liu Z (2023) Alternative Splicing in the Regulatory Circuit of Plant Temperature Response. Int J Mol Sci 24.
[34] Yeap WC, Namasivayam P, Ho CL (2014) HnRNP-like proteins as post-transcriptional regulators. Plant Sci 227: 90-100.
[35] Zhang C, Gschwend AR, Ouyang Y, Long M (2014) Evolution of gene structural complexity: an alternative-splicing-based model accounts for intron-containing retrogenes. Plant Physiol 165: 412-423.
[36] Zhang G, Guo G, Hu X, Zhang Y, Li Q, Li R, Zhuang R, Lu Z, He Z, Fang X, Chen L, Tian W, Tao Y, Kristiansen K, Zhang X, Li S, Yang H, Wang J (2010) Deep RNA sequencing at single base-pair resolution reveals high complexity of the rice transcriptome. Genome Res 20: 646-654.
[37] Zhang Z, Xiao B (2018) Comparative alternative splicing analysis of two contrasting rice cultivars under drought stress and association of differential splicing genes with drought response QTLs. Euphytica 214: 73.
Cite This Article
  • APA Style

    Fangyu Zhang, Zhengfeng Zhang, Enci Wang, Chengqi Wang, Benze Xiao. (2023). The Importance of Stiff Change of U(T) Content Around Splicing Sites in Efficient Plant Intron Splicing -- A Case Study in Rice. Computational Biology and Bioinformatics, 11(1), 13-18. https://doi.org/10.11648/j.cbb.20231101.12

    Copy | Download

    ACS Style

    Fangyu Zhang; Zhengfeng Zhang; Enci Wang; Chengqi Wang; Benze Xiao. The Importance of Stiff Change of U(T) Content Around Splicing Sites in Efficient Plant Intron Splicing -- A Case Study in Rice. Comput. Biol. Bioinform. 2023, 11(1), 13-18. doi: 10.11648/j.cbb.20231101.12

    Copy | Download

    AMA Style

    Fangyu Zhang, Zhengfeng Zhang, Enci Wang, Chengqi Wang, Benze Xiao. The Importance of Stiff Change of U(T) Content Around Splicing Sites in Efficient Plant Intron Splicing -- A Case Study in Rice. Comput Biol Bioinform. 2023;11(1):13-18. doi: 10.11648/j.cbb.20231101.12

    Copy | Download

  • @article{10.11648/j.cbb.20231101.12,
      author = {Fangyu Zhang and Zhengfeng Zhang and Enci Wang and Chengqi Wang and Benze Xiao},
      title = {The Importance of Stiff Change of U(T) Content Around Splicing Sites in Efficient Plant Intron Splicing -- A Case Study in Rice},
      journal = {Computational Biology and Bioinformatics},
      volume = {11},
      number = {1},
      pages = {13-18},
      doi = {10.11648/j.cbb.20231101.12},
      url = {https://doi.org/10.11648/j.cbb.20231101.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cbb.20231101.12},
      abstract = {Pre-mRNAs splicing is one of the fundamental process which generates multiple transcripts from a single gene, contributing to transcriptome and proteome diversity. AS is regulated by the cooperation of trans-factors and cis-elements. In plants, extensive alternative splicing occurs not only in tissue-specific manner but also in response to stress conditions. Intron retention is the most predominant splicing type. However, the cis-elements regulating intron retention are still ambiguous in plants, especially under environmental stresses. This study aimed to elucidate the cis-elements underlying intron retention in plants under adverse enrironments. Using RNA-seq data of rice cultivars IRAT109 and ZS97 under drought environments, we compared the sequence characteristics between constitutive and retained introns. The results show that the main AS types include intron retention (IR), alternative acceptor sites (AA), alternative donor sites (AD) and cassette exon (exon skipping, ES). Among of them, IR was the prevelent pattern with frequencies of 30.8-31.2%. Motif analysis of 5' and 3' 200bp intron sequences found rich U(T) in the motifs for both constitutive and retained introns. By further analysis of base composition of sequences flanking splice sites, we detected a notable difference in U(T) content between introns and their neighboring exons in constitutive introns, but not in retained introns. The results in this study suggested that the lack of significant changes in U(T) content between retained introns and neighboring exons might be a potential cis feature of intron retention.},
     year = {2023}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - The Importance of Stiff Change of U(T) Content Around Splicing Sites in Efficient Plant Intron Splicing -- A Case Study in Rice
    AU  - Fangyu Zhang
    AU  - Zhengfeng Zhang
    AU  - Enci Wang
    AU  - Chengqi Wang
    AU  - Benze Xiao
    Y1  - 2023/06/05
    PY  - 2023
    N1  - https://doi.org/10.11648/j.cbb.20231101.12
    DO  - 10.11648/j.cbb.20231101.12
    T2  - Computational Biology and Bioinformatics
    JF  - Computational Biology and Bioinformatics
    JO  - Computational Biology and Bioinformatics
    SP  - 13
    EP  - 18
    PB  - Science Publishing Group
    SN  - 2330-8281
    UR  - https://doi.org/10.11648/j.cbb.20231101.12
    AB  - Pre-mRNAs splicing is one of the fundamental process which generates multiple transcripts from a single gene, contributing to transcriptome and proteome diversity. AS is regulated by the cooperation of trans-factors and cis-elements. In plants, extensive alternative splicing occurs not only in tissue-specific manner but also in response to stress conditions. Intron retention is the most predominant splicing type. However, the cis-elements regulating intron retention are still ambiguous in plants, especially under environmental stresses. This study aimed to elucidate the cis-elements underlying intron retention in plants under adverse enrironments. Using RNA-seq data of rice cultivars IRAT109 and ZS97 under drought environments, we compared the sequence characteristics between constitutive and retained introns. The results show that the main AS types include intron retention (IR), alternative acceptor sites (AA), alternative donor sites (AD) and cassette exon (exon skipping, ES). Among of them, IR was the prevelent pattern with frequencies of 30.8-31.2%. Motif analysis of 5' and 3' 200bp intron sequences found rich U(T) in the motifs for both constitutive and retained introns. By further analysis of base composition of sequences flanking splice sites, we detected a notable difference in U(T) content between introns and their neighboring exons in constitutive introns, but not in retained introns. The results in this study suggested that the lack of significant changes in U(T) content between retained introns and neighboring exons might be a potential cis feature of intron retention.
    VL  - 11
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, People’s Republic of China

  • Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, People’s Republic of China

  • Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, People’s Republic of China

  • College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, People’s Republic of China

  • College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, People’s Republic of China

  • Sections