Transposons Acting As Competitive Endogenous RNAs: In-Silico Evidence from Datasets Characterised by L1 Overexpression

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2022 Dec 23

PMID 36552034

Authors

Mauro Esposito

Nicolo Gualandi

Giovanni Spirito

Federico Ansaloni

Stefano Gustincich

Remo Sanges

Affiliations

Soon will be listed here.

Abstract

LINE L1 are transposable elements that can replicate within the genome by passing through RNA intermediates. The vast majority of these element copies in the human genome are inactive and just between 100 and 150 copies are still able to mobilize. During evolution, they could have been positively selected for beneficial cellular functions. Nonetheless, L1 deregulation can be detrimental to the cell, causing diseases such as cancer. The activity of miRNAs represents a fundamental mechanism for controlling transcript levels in somatic cells. These are a class of small non-coding RNAs that cause degradation or translational inhibition of their target transcripts. Beyond this, competitive endogenous RNAs (ceRNAs), mostly made by circular and non-coding RNAs, have been seen to compete for the binding of the same set of miRNAs targeting protein coding genes. In this study, we have investigated whether autonomously transcribed L1s may act as ceRNAs by analyzing public dataset in-silico. We observed that genes sharing miRNA target sites with L1 have a tendency to be upregulated when L1 are overexpressed, suggesting the possibility that L1 might act as ceRNAs. This finding will help in the interpretation of transcriptomic responses in contexts characterized by the specific activation of transposons.

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References

Johnson R, Guigo R . The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs. RNA. 2014; 20(7):959-76. PMC: 4114693. DOI: 10.1261/rna.044560.114. View

Jordan I, Rogozin I, Glazko G, Koonin E . Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends Genet. 2003; 19(2):68-72. DOI: 10.1016/s0168-9525(02)00006-9. View

Jo M, Shin S, Jung S, Kim E, Song J, Hohng S . Human Argonaute 2 Has Diverse Reaction Pathways on Target RNAs. Mol Cell. 2015; 59(1):117-24. DOI: 10.1016/j.molcel.2015.04.027. View

Hamdorf M, Idica A, Zisoulis D, Gamelin L, Martin C, Sanders K . miR-128 represses L1 retrotransposition by binding directly to L1 RNA. Nat Struct Mol Biol. 2015; 22(10):824-31. DOI: 10.1038/nsmb.3090. View

De Cecco M, Ito T, Petrashen A, Elias A, Skvir N, Criscione S . L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature. 2019; 566(7742):73-78. PMC: 6519963. DOI: 10.1038/s41586-018-0784-9. View

Rivas F, Tolia N, Song J, Aragon J, Liu J, Hannon G . Purified Argonaute2 and an siRNA form recombinant human RISC. Nat Struct Mol Biol. 2005; 12(4):340-9. DOI: 10.1038/nsmb918. View

Lander E, Linton L, Birren B, Nusbaum C, Zody M, Baldwin J . Initial sequencing and analysis of the human genome. Nature. 2001; 409(6822):860-921. DOI: 10.1038/35057062. View

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

Roush S, Slack F . The let-7 family of microRNAs. Trends Cell Biol. 2008; 18(10):505-16. DOI: 10.1016/j.tcb.2008.07.007. View

10.

Ni J, Grate L, Donohue J, Preston C, Nobida N, OBrien G . Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay. Genes Dev. 2007; 21(6):708-18. PMC: 1820944. DOI: 10.1101/gad.1525507. View

11.

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

12.

Kolberg L, Raudvere U, Kuzmin I, Vilo J, Peterson H . gprofiler2 -- an R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler. F1000Res. 2021; 9. PMC: 7859841. DOI: 10.12688/f1000research.24956.2. View

13.

Ardeljan D, Steranka J, Liu C, Li Z, Taylor M, Payer L . Cell fitness screens reveal a conflict between LINE-1 retrotransposition and DNA replication. Nat Struct Mol Biol. 2020; 27(2):168-178. PMC: 7080318. DOI: 10.1038/s41594-020-0372-1. View

14.

Gualandi N, Iperi C, Esposito M, Ansaloni F, Gustincich S, Sanges R . Meta-Analysis Suggests That Intron Retention Can Affect Quantification of Transposable Elements from RNA-Seq Data. Biology (Basel). 2022; 11(6). PMC: 9220773. DOI: 10.3390/biology11060826. View

15.

De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C . The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature. 2011; 480(7376):259-63. DOI: 10.1038/nature10547. View

16.

Morrish T, Gilbert N, Myers J, Vincent B, Stamato T, Taccioli G . DNA repair mediated by endonuclease-independent LINE-1 retrotransposition. Nat Genet. 2002; 31(2):159-65. DOI: 10.1038/ng898. View

17.

Hubley R, Finn R, Clements J, Eddy S, Jones T, Bao W . The Dfam database of repetitive DNA families. Nucleic Acids Res. 2015; 44(D1):D81-9. PMC: 4702899. DOI: 10.1093/nar/gkv1272. View

18.

Wee L, Flores-Jasso C, Salomon W, Zamore P . Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties. Cell. 2012; 151(5):1055-67. PMC: 3595543. DOI: 10.1016/j.cell.2012.10.036. View

19.

Lee R, Ambros V . An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001; 294(5543):862-4. DOI: 10.1126/science.1065329. View

20.

Servant G, Streva V, Derbes R, Wijetunge M, Neeland M, White T . The Nucleotide Excision Repair Pathway Limits L1 Retrotransposition. Genetics. 2017; 205(1):139-153. PMC: 5223499. DOI: 10.1534/genetics.116.188680. View