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Cited by 592Chromosomal and Genetic VariationsGenomic variations and chromosomal abnormalitiesGenome Rearrangement Algorithms

Active human retrotransposons: variation and disease

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Hancks, Dustin C, Kazazian, Haig H·2012·Current Opinion in Genetics & Development
DOI 10.1016/j.gde.2012.02.006PMC PMC3376660
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Abstract

Mobile DNAs, also known as transposons or 'jumping genes', are widespread in nature and comprise an estimated 45% of the human genome. Transposons are divided into two general classes based on their transposition intermediate (DNA or RNA). Only one subclass, the non-LTR retrotransposons, which includes the Long INterspersed Element-1 (LINE-1 or L1), is currently active in humans as indicated by 96 disease-causing insertions. The autonomous LINE-1 is capable of retrotransposing not only a copy of its own RNA in cis but also other RNAs (Alu, SINE-VNTR-Alu (SVA), U6) in trans to new genomic locations through an element encoded reverse transcriptase. L1 can also retrotranspose cellular mRNAs, resulting in processed pseudogene formation. Here, we highlight recent reports that update our understanding of human L1 retrotransposition and their role in disease. Finally we discuss studies that provide insights into the past and current activity of these retrotransposons, and shed light on not just when, but where, retrotransposition occurs and its part in genetic variation.

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Crossref · 10.1016/j.gde.2012.02.006

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  • L1 activity has been implicated in a variety of age-related disorders, including cancer and neurodegeneration.

    “L1 activity has been implicated in a variety of age-related disorders12, including cancer7,13 and neurodegeneration14,15.”

    From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [12]

    The INSERTIONS AND DISEASE section reports multiple disease-causing retrotransposon insertions, and TIMING OF RETROTRANSPOSITION says somatic L1 activity may play a role in tumorigenesis. But the copy does not characterize these as age-related disorders or link L1 activity to neurodegeneration; its discussion of brain activity mentions Rett syndrome instead. In the citing sentence, the separate cancer and neurodegeneration citations do not establish those points for this source. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Some non-LTR elements (SINE and SVA) retain mobilization potential when LINE-1 reverse transcriptase is present.

    “some of these elements retain mobilization potential when LINE-1 reverse transcriptase is present”

    From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Hancks & Kazazian 2012

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Cited by

Sorted by citations

Authors
Hancks, D. C., & Kazazian, H. H.
Affiliations
Johns Hopkins University (US)
Corresponding author
Kazazian, Haig H
ORCID
Hancks, Dustin C
Venue
Current Opinion in Genetics & Development
Publisher
Elsevier BV
Published
2012-06
Volume
22
Issue
3
Pages
191-203
ISSN
0959-437X (ISSN-L)
DOI
10.1016/j.gde.2012.02.006
PMC
PMC3376660
OpenAlex
W2040741651
Cited by
592
References
8
Citations by year
2026: 15 · 2025: 16 · 2024: 28 · 2023: 25 · 2022: 37 · 2021: 38 · 2020: 39 · 2019: 39 · 2018: 40 · 2017: 59 · 2016: 71 · 2015: 54 · 2014: 59 · 2013: 51 · 2012: 18
FWCI
6.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Genetics & Development (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R01GM099875, R01GM045398)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
Keywords
LINE-1 retrotransposons, retrotransposition, mobile DNA, Alu elements, reverse transcriptase, genetic variation, transposable element activity
MeSH terms
DNA Transposable Elements, Humans, Promoter Regions, Genetic, Pseudogenes, RNA, Time Factors, Transcription, Genetic, Genetic Variation, Genome, Human, Open Reading Frames, DNA Methylation, Long Interspersed Nucleotide Elements, Alu Elements, Untranslated Regions, Genetic Diseases, Inborn

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