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Identification Of Long Non-coding RNAs Of Vlinc Class

Posted on:2018-03-07Degree:MasterType:Thesis
Country:ChinaCandidate:D D CaiFull Text:PDF
GTID:2310330536974657Subject:Polymer Chemistry and Physics
Abstract/Summary:PDF Full Text Request
Large-scale genome sequencing has led to a better understanding of the genomic structure of human genome,showing that only about 2% of the human genome is encoding proteins,while the vast majority is non-coding regions.Based on its size,non-coding RNA can be divided into two classes,one is small non-coding RNA(sncRNA)which is less than 200 nt and the other is long non-coding RNA(lncRNA)which is more than 200 nt.Recently,a large number of lncRNAs have been reported,and showed that they can participate in regulating the body's DNA damage,DNA replication,cell proliferation,cell differentiation,apoptosis and so on.Its rich biological characteristics is closely related to the occurrence of cancers,but the specific mechanism is not clear yet.This paper uses the advanced single molecule sequencing technology(SMS)on the study of the injury of K562 cells induced by DNA damage drugs treatment to screen out a special kind of lnc RNAs.This is long non-coding RNAs that are transcribed from non-coding DNA sequences between protein-coding genes(very long integenic non-coding RNA,vlincRNA).The results show that vlincRNA promoters have a tendency to contain sequences of endogenous retroviruses at LTR region.Strikingly,LTR-driven vlincRNAs are enriched in embryonic stem cells and cancerous cells.VlincRNAs can be syntenically conserved in humans and mouse and their depletion using RNAi can cause apoptosis in cancerous cells.Therefore,the potential function of vlincRNA in DNA damage response will offer a new study of cancer therapy.In this paper,the identification of potential functions of several vlincRNAs in DNA damage response is carried out by the application of SMS,Genome Map,qPCR and Gene Ontology(GO)analysis.After repeated screening of the vlincRNAs data,I validated expression of 4 such vlincRNAs: Vlinc KVURN1,Vlinc KVDRN2,Vlinc KVURN3,Vlinc KVDRN4.The expression change was validated in 3 independent biological replicas for all 4 vlincRNAs:two up-regulated and two down-regulated.And all 4 vlincRNAs are likely regulated by LTR-containing promoters.Some vlincRNAs are separate from known annotations,such are part of very complex regions overlapping known genes.Systems biology analysis of suggests that these vlincRNAs correlate with genes involved in functions consistent with their involvement in DNA damage response.
Keywords/Search Tags:Lnc RNA, DNA damage, SMS, VlincRNA, GO analysis
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