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Current Bioinformatics

Editor-in-Chief

ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

Association Analysis Between Introns and mRNAs in Caenorhabditis elegans Genes with Different Expression Levels

Author(s): Yanjuan Cao, Qiang Zhang*, Zuwei Yan* and Xiaoqing Zhao

Volume 17, Issue 3, 2022

Published on: 20 January, 2022

Page: [263 - 272] Pages: 10

DOI: 10.2174/1574893616666211207143600

Price: $65

Abstract

Background: Introns are ubiquitous in pre-mRNA but are often overlooked. They also play an important role in the regulation of gene expression.

Objective and Methods: We mainly use the improved Smith-Waterman local alignment approach to compare the optimal matching regions between introns and mRNA sequences in Caenorhabditis elegans (C. elegans) genes with high and low expression.

Results: We found that the relative matching frequency distributions of all genes lie exactly between highly and lowly expressed genes, indicating that introns in highly and lowly expressed genes have different biological functions. Highly expressed genes have higher matching strengths on mRNA sequences than genes expressed at lower levels; the remarkably matched regions appear in UTR regions, particularly in the 3'UTR. The optimal matching frequency distributions have obvious differences in functional regions of the translation initiation and termination sites in highly and lowly expressed genes. The mRNA sequences with CpG islands tend to have stronger relative matching frequency distributions, especially in highly expressed genes. Additionally, the sequence characteristics of the optimal matched segments are consistent with those of the miRNAs, and they are considered a type of functional RNA segment.

Conclusion: Introns in highly and lowly expressed genes contribute to the recognition translation initiation sites and translation termination sites. Moreover, our results suggest that the potential matching relationships between introns and mRNA sequences in highly and lowly expressed genes are significantly different and indicate that the matching strength correlates with the ability of introns to enhance gene expression.

Keywords: Introns, highly expressed genes, lowly expressed genes, mRNA sequences, optimal matched segments, CpG islands.

Graphical Abstract

[1]
Sambrook J. Adenovirus amazes at Cold Spring Harbor. Nature 1977; 268(5616): 101-4.
[http://dx.doi.org/10.1038/268101a0] [PMID: 593301]
[2]
Irimia M, Roy SW. Origin of spliceosomal introns and alternative splicing. Cold Spring Harb Perspect Biol 2014; 6(6): a016071.
[http://dx.doi.org/10.1101/cshperspect.a016071] [PMID: 24890509]
[3]
Csuros M, Rogozin IB, Koonin EV. A detailed history of intron-rich eukaryotic ancestors inferred from a global survey of 100 complete genomes. PLOS Comput Biol 2011; 7(9): e1002150.
[http://dx.doi.org/10.1371/journal.pcbi.1002150] [PMID: 21935348]
[4]
Chorev M, Carmel L. The function of introns. Front Genet 2012; 3: 55.
[http://dx.doi.org/10.3389/fgene.2012.00055] [PMID: 22518112]
[5]
Chorev M, Joseph Bekker A, Goldberger J, Carmel L. Identification of introns harboring functional sequence elements through positional conservation. Sci Rep 2017; 7(1): 4201.
[http://dx.doi.org/10.1038/s41598-017-04476-0] [PMID: 28646210]
[6]
Moore MJ, Proudfoot NJ. Pre-mRNA processing reaches back to transcription and ahead to translation. Cell 2009; 136(4): 688-700.
[http://dx.doi.org/10.1016/j.cell.2009.02.001] [PMID: 19239889]
[7]
Buchman AR, Berg P. Comparison of intron-dependent and intron-independent gene expression. Mol Cell Biol 1988; 8(10): 4395-405.
[PMID: 3185553]
[8]
Le Hir H, Nott A, Moore MJ. How introns influence and enhance eukaryotic gene expression. Trends Biochem Sci 2003; 28(4): 215-20.
[http://dx.doi.org/10.1016/S0968-0004(03)00052-5] [PMID: 12713906]
[9]
Shaul O. How introns enhance gene expression. Int J Biochem Cell Biol 2017; 91(Pt B): 145-55.
[http://dx.doi.org/10.1016/j.biocel.2017.06.016] [PMID: 28673892]
[10]
Maas C, Laufs J, Grant S, Korfhage C, Werr W. The combination of a novel stimulatory element in the first exon of the maize Shrunken-1 gene with the following intron 1 enhances reporter gene expression up to 1000-fold. Plant Mol Biol 1991; 16(2): 199-207.
[http://dx.doi.org/10.1007/BF00020552] [PMID: 1893097]
[11]
Crane MM, Sands B, Battaglia C, et al. In vivo measurements reveal a single 5'-intron is sufficient to increase protein expression level in Caenorhabditis elegans. Sci Rep 2019; 9(1): 9192.
[http://dx.doi.org/10.1038/s41598-019-45517-0] [PMID: 31235724]
[12]
Kwek KY, Murphy S, Furger A, et al. U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nat Struct Biol 2002; 9(11): 800-5.
[http://dx.doi.org/10.1038/nsb862] [PMID: 12389039]
[13]
Samadder P, Sivamani E, Lu J, Li X, Qu R. Transcriptional and post-transcriptional enhancement of gene expression by the 5' UTR intron of rice rubi3 gene in transgenic rice cells. Mol Genet Genomics 2008; 279(4): 429-39.
[http://dx.doi.org/10.1007/s00438-008-0323-8] [PMID: 18236078]
[14]
Gudikote JP, Imam JS, Garcia RF, Wilkinson MF. RNA splicing promotes translation and RNA surveillance. Nat Struct Mol Biol 2005; 12(9): 801-9.
[http://dx.doi.org/10.1038/nsmb980] [PMID: 16116435]
[15]
Bourdon V, Harvey A, Lonsdale DM. Introns and their positions affect the translational activity of mRNA in plant cells. EMBO Rep 2001; 2(5): 394-8.
[http://dx.doi.org/10.1093/embo-reports/kve090] [PMID: 11375930]
[16]
Hoshida H, Kondo M, Kobayashi T, Yarimizu T, Akada R. 5´-UTR introns enhance protein expression in the yeast Saccharomyces cere-visiae. Appl Microbiol Biotechnol 2017; 101(1): 241-51.
[http://dx.doi.org/10.1007/s00253-016-7891-z] [PMID: 27734122]
[17]
Laxa M. Intron-Mediated Enhancement: A tool for heterologous gene expression in plants. Front Plant Sci 2017; 7: 1977.
[http://dx.doi.org/10.3389/fpls.2016.01977] [PMID: 28111580]
[18]
Henricson A, Forslund K, Sonnhammer EL. Orthology confers intron position conservation. BMC Genomics 2010; 11: 412.
[http://dx.doi.org/10.1186/1471-2164-11-412] [PMID: 20598118]
[19]
Parra G, Bradnam K, Rose AB, Korf I. Comparative and functional analysis of intron-mediated enhancement signals reveals conserved features among plants. Nucleic Acids Res 2011; 39(13): 5328-37.
[http://dx.doi.org/10.1093/nar/gkr043] [PMID: 21427088]
[20]
Zhang Q, Li H, Zhao X, et al. Analysis on the preference for sequence matching between mRNA sequences and the corresponding introns in ribosomal protein genes. J Theor Biol 2016; 392: 113-21.
[http://dx.doi.org/10.1016/j.jtbi.2015.12.003] [PMID: 26707402]
[21]
Reed R, Hurt E. A conserved mRNA export machinery coupled to pre-mRNA splicing. Cell 2002; 108(4): 523-31.
[http://dx.doi.org/10.1016/S0092-8674(02)00627-X] [PMID: 11909523]
[22]
Le Hir H, Saulière J, Wang Z. The exon junction complex as a node of post-transcriptional networks. Nat Rev Mol Cell Biol 2016; 17(1): 41-54.
[http://dx.doi.org/10.1038/nrm.2015.7] [PMID: 26670016]
[23]
Nott A, Le Hir H, Moore MJ. Splicing enhances translation in mammalian cells: An additional function of the exon junction complex. Genes Dev 2004; 18(2): 210-22.
[http://dx.doi.org/10.1101/gad.1163204] [PMID: 14752011]
[24]
Lee HC, Choe J, Chi SG, Kim YK. Exon junction complex enhances translation of spliced mRNAs at multiple steps. Biochem Biophys Res Commun 2009; 384(3): 334-40.
[http://dx.doi.org/10.1016/j.bbrc.2009.04.123] [PMID: 19409878]
[25]
Isken O, Maquat LE. Quality control of eukaryotic mRNA: Safeguarding cells from abnormal mRNA function. Genes Dev 2007; 21(15): 1833-56.
[http://dx.doi.org/10.1101/gad.1566807] [PMID: 17671086]
[26]
Brogna S, Wen J. Nonsense-mediated mRNA decay (NMD) mechanisms. Nat Struct Mol Biol 2009; 16(2): 107-13.
[http://dx.doi.org/10.1038/nsmb.1550] [PMID: 19190664]
[27]
Zhao X, Li H, Bao T. Analysis on the interaction between post-spliced introns and corresponding protein coding sequences in ribosomal protein genes. J Theor Biol 2013; 328: 33-42.
[http://dx.doi.org/10.1016/j.jtbi.2013.03.002] [PMID: 23499990]
[28]
Bo S, Li H, Zhang Q, Lu Z, Bao T, Zhao X. Potential relations between post-spliced introns and mature mRNAs in the Caenorhabditis elegans genome. J Theor Biol 2019; 467: 7-14.
[http://dx.doi.org/10.1016/j.jtbi.2019.01.031] [PMID: 30710554]
[29]
Zhang Q, Zhao XQ, Bo SL, et al. Conservative analysis on matching between mRNA and corresponding intron. Chinese J Bioinform 2020; 3: 149-56.
[30]
Zhang Q, Li H, Zhao X, Zheng Y, Zhou D. Distribution bias of the sequence matching between exons and introns in exon joint and EJC binding region in C. elegans. J Theor Biol 2015; 364: 295-304.
[http://dx.doi.org/10.1016/j.jtbi.2014.09.009] [PMID: 25234235]
[31]
Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol 1987; 196(2): 261-82.
[http://dx.doi.org/10.1016/0022-2836(87)90689-9] [PMID: 3656447]
[32]
Fullerton SM, Bernardo Carvalho A, Clark AG. Local rates of recombination are positively correlated with GC content in the human ge-nome. Mol Biol Evol 2001; 18(6): 1139-42.
[http://dx.doi.org/10.1093/oxfordjournals.molbev.a003886] [PMID: 11371603]
[33]
Cao Y, Wang Y, Li Y, Yang J, Ma L. The Arabidopsis AGAMOUS 5'-UTR represses downstream gene translation. Sci China Life Sci 2019; 62(2): 272-5.
[http://dx.doi.org/10.1007/s11427-018-9383-y] [PMID: 30421295]
[34]
Vinogradov AE. Dualism of gene GC content and CpG pattern in regard to expression in the human genome: Magnitude versus breadth. Trends Genet 2005; 21(12): 639-43.
[http://dx.doi.org/10.1016/j.tig.2005.09.002] [PMID: 16202472]
[35]
Pasquinelli AE. MicroRNAs and their targets: Recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 2012; 13(4): 271-82.
[http://dx.doi.org/10.1038/nrg3162] [PMID: 22411466]
[36]
Das S, Bansal M. Variation of gene expression in plants is influenced by gene architecture and structural properties of promoters. PLoS One 2019; 14(3): e0212678.
[http://dx.doi.org/10.1371/journal.pone.0212678] [PMID: 30908494]
[37]
Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP. MicroRNA targeting specificity in mammals: Determinants be-yond seed pairing. Mol Cell 2007; 27(1): 91-105.
[http://dx.doi.org/10.1016/j.molcel.2007.06.017] [PMID: 17612493]
[38]
Kaufman EJ, Miska EA. The microRNAs of Caenorhabditis elegans. Semin Cell Dev Biol 2010; 21(7): 728-37.
[http://dx.doi.org/10.1016/j.semcdb.2010.07.001] [PMID: 20637886]
[39]
Rao YS, Chai XW, Wang ZF, Nie QH, Zhang XQ. Impact of GC content on gene expression pattern in chicken. Genet Sel Evol 2013; 45: 9.
[http://dx.doi.org/10.1186/1297-9686-45-9] [PMID: 23557030]
[40]
Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell 2009; 136(2): 215-33.
[http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID: 19167326]
[41]
Watanabe T, Totoki Y, Toyoda A, et al. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 2008; 453(7194): 539-43.
[http://dx.doi.org/10.1038/nature06908] [PMID: 18404146]
[42]
Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: From microRNA sequences to function. Nucleic Acids Res 2019; 47(D1): D155-62.
[http://dx.doi.org/10.1093/nar/gky1141] [PMID: 30423142]

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