A 3′ Poly(A) Tract Is Required for LINE-1 Retrotransposition

Doucet, Aurélien J.; Wilusz, Jeremy E.; Miyoshi, Tomoichiro; Liu, Ying; Moran, John V.

doi:10.1016/j.molcel.2015.10.012

Cited by 126 publications

(152 citation statements)

References 69 publications

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…Alu elements require a polyA-tail for their retrotransposition (Doucet et al, 2015), and therefore, when they insert into other genes in an antisense orientation, they start with a polyuridine tract (U-tract). Moreover, these antisense Alu elements often contain cryptic splice sites (Lev-Maor et al., 2003).…”

Section: Introductionmentioning

confidence: 99%

Splicing repression allows the gradual emergence of new Alu-exons in primate evolution

Attig

Mozos²,

Haberman³

et al. 2016

eLife

View full text Add to dashboard Cite

Alu elements are retrotransposons that frequently form new exons during primate evolution. Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exons. We identify 3100 new Alu-exons and show that NMD more efficiently recognises transcripts with Alu-exons compared to other exons with premature termination codons. However, some Alu-exons escape NMD, especially when an adjacent intron is retained, highlighting the importance of concerted repression by splicing and NMD. We show that evolutionary progression of 3' splice sites is coupled with longer repressive uridine tracts. Once the 3' splice site at ancient Alu-exons reaches a stable phase, splicing repression by hnRNPC decreases, but the exons generally remain sensitive to NMD. We conclude that repressive motifs are strongest next to cryptic exons and that gradual weakening of these motifs contributes to the evolutionary emergence of new alternative exons.DOI: http://dx.doi.org/10.7554/eLife.19545.001

show abstract

Section: Introductionmentioning

confidence: 99%

Splicing repression allows the gradual emergence of new Alu-exons in primate evolution

Attig

Mozos²,

Haberman³

et al. 2016

eLife

View full text Add to dashboard Cite

show abstract

“…Endonuclease-independent (ENi) L1 mobilisation can also occur into pre-existing DNA double strand breaks, producing insertions that lack TPRT hallmarks [21–24]. Notably, L1 can mobilise other polyadenylated RNAs, such as Alu retrotransposons, in trans [25–27]. L1 and Alu elements can also participate in DNA rearrangements driven by recombination [28, 29].…”

Section: Introductionmentioning

confidence: 99%

Evidence for L1-associated DNA rearrangements and negligible L1 retrotransposition in glioblastoma multiforme

Carreira

Ewing

et al. 2016

Mobile DNA

View full text Add to dashboard Cite

BackgroundLINE-1 (L1) retrotransposons are a notable endogenous source of mutagenesis in mammals. Notably, cancer cells can support unusual L1 retrotransposition and L1-associated sequence rearrangement mechanisms following DNA damage. Recent reports suggest that L1 is mobile in epithelial tumours and neural cells but, paradoxically, not in brain cancers.ResultsHere, using retrotransposon capture sequencing (RC-seq), we surveyed L1 mutations in 14 tumours classified as glioblastoma multiforme (GBM) or as a lower grade glioma. In four GBM tumours, we characterised one probable endonuclease-independent L1 insertion, two L1-associated rearrangements and one likely Alu-Alu recombination event adjacent to an L1. These mutations included PCR validated intronic events in MeCP2 and EGFR. Despite sequencing L1 integration sites at up to 250× depth by RC-seq, we found no tumour-specific, endonuclease-dependent L1 insertions. Whole genome sequencing analysis of the tumours carrying the MeCP2 and EGFR L1 mutations also revealed no endonuclease-dependent L1 insertions. In a complementary in vitro assay, wild-type and endonuclease mutant L1 reporter constructs each mobilised very inefficiently in four cultured GBM cell lines.ConclusionsThese experiments altogether highlight the consistent absence of canonical L1 retrotransposition in GBM tumours and cultured cell lines, as well as atypical L1-associated sequence rearrangements following DNA damage in vivo.Electronic supplementary materialThe online version of this article (doi:10.1186/s13100-016-0076-6) contains supplementary material, which is available to authorized users.

show abstract

“…It contains a polypurine tract that potentially could form a G-quadruplex structure [13], but the function of this sequence remains unknown. L1 ends with a poly-A tail that was shown to be critical for L1 retrotransposition [14]. Short direct repeats, flanking a transposon, are generated from the target DNA sequence during the L1 integration.…”

Section: Introductionmentioning

confidence: 99%

“…It was suggested that this effect may play an important role in maintaining activity of Alu elements [32]. It was experimentally confirmed that the poly-A tail is essential for L1 retrotransposition [14]. Recognition of poly-A tail by LINE retrotransposition machinery could explain formation of the processed pseudogenes [34], however many processed pseudogenes, lacking poly-A tails and derived from nearly all types of RNA, were found in various genomes [35, 36].…”

Section: Introductionmentioning

confidence: 99%

Conserved 3′ UTR stem-loop structure in L1 and Alu transposons in human genome: possible role in retrotransposition

Grechishnikova

Poptsova

2016

BMC Genomics

View full text Add to dashboard Cite

BackgroundIn the process of retrotransposition LINEs use their own machinery for copying and inserting themselves into new genomic locations, while SINEs are parasitic and require the machinery of LINEs. The exact mechanism of how a LINE-encoded reverse transcriptase (RT) recognizes its own and SINE RNA remains unclear. However it was shown for the stringent-type LINEs that recognition of a stem-loop at the 3′UTR by RT is essential for retrotransposition. For the relaxed-type LINEs it is believed that the poly-A tail is a common recognition element between LINE and SINE RNA. However polyadenylation is a property of any messenger RNA, and how the LINE RT recognizes transposon and non-transposon RNAs remains an open question. It is likely that RNA secondary structures play an important role in RNA recognition by LINE encoded proteins.ResultsHere we selected a set of L1 and Alu elements from the human genome and investigated their sequences for the presence of position-specific stem-loop structures. We found highly conserved stem-loop positions at the 3′UTR. Comparative structural analyses of a human L1 3′UTR stem-loop showed a similarity to 3′UTR stem-loops of the stringent-type LINEs, which were experimentally shown to be recognized by LINE RT. The consensus stem-loop structure consists of 5–7 bp loop, 8–10 bp stem with a bulge at a distance of 4–6 bp from the loop. The results show that a stem loop with a bulge exists at the 3′-end of Alu. We also found conserved stem-loop positions at 5′UTR and at the end of ORF2 and discuss their possible role.ConclusionsHere we presented an evidence for the presence of a highly conserved 3′UTR stem-loop structure in L1 and Alu retrotransposons in the human genome. Both stem-loops show structural similarity to the stem-loops of the stringent-type LINEs experimentally confirmed as essential for retrotransposition. Here we hypothesize that both L1 and Alu RNA are recognized by L1 RT via the 3′-end RNA stem-loop structure. Other conserved stem-loop positions in L1 suggest their possible functions in protein-RNA interactions but to date no experimental evidence has been reported.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3344-4) contains supplementary material, which is available to authorized users.

show abstract

A 3′ Poly(A) Tract Is Required for LINE-1 Retrotransposition

Cited by 126 publications

References 69 publications

Splicing repression allows the gradual emergence of new Alu-exons in primate evolution

Splicing repression allows the gradual emergence of new Alu-exons in primate evolution

Evidence for L1-associated DNA rearrangements and negligible L1 retrotransposition in glioblastoma multiforme

Conserved 3′ UTR stem-loop structure in L1 and Alu transposons in human genome: possible role in retrotransposition

Contact Info

Product

Resources

About