Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement

Abstract L1 (LINE1) non-LTR retrotransposons are ubiquitous genomic parasites and the dominant transposable element in humans having generated about 40% of their genomic DNA during their ~ 100 million years (Myr) of activity in primates. L1 replicates in germ line cells and early embryos, causing ge...

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Main Authors: Nikola A. Mizgier, Charlie E. Jones, Anthony V. Furano
Format: Article
Language:English
Published: BMC 2023-10-01
Series:Mobile DNA
Subjects:
Online Access:https://doi.org/10.1186/s13100-023-00303-8
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author Nikola A. Mizgier
Charlie E. Jones
Anthony V. Furano
author_facet Nikola A. Mizgier
Charlie E. Jones
Anthony V. Furano
author_sort Nikola A. Mizgier
collection DOAJ
description Abstract L1 (LINE1) non-LTR retrotransposons are ubiquitous genomic parasites and the dominant transposable element in humans having generated about 40% of their genomic DNA during their ~ 100 million years (Myr) of activity in primates. L1 replicates in germ line cells and early embryos, causing genetic diversity and defects, but can be active in some somatic stem cells, tumors and during aging. L1 encodes two proteins essential for retrotransposition: ORF2p, a reverse transcriptase that contains an endonuclease domain, and ORF1p, a coiled coil mediated homo trimer, which functions as a nucleic acid chaperone. Both proteins contain highly conserved domains and preferentially bind their encoding transcript to form an L1 ribonucleoprotein (RNP), which mediates retrotransposition. However, the coiled coil has periodically undergone episodes of substantial amino acid replacement to the extent that a given L1 family can concurrently express multiple ORF1s that differ in the sequence of their coiled coils. Here we show that such distinct ORF1p sequences can become entangled forming heterotrimers when co-expressed from separate vectors and speculate on how coiled coil entanglement could affect coiled coil evolution.
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spelling doaj.art-68c4bc9776bd459cb5e16c9588d5eda52023-11-26T13:34:29ZengBMCMobile DNA1759-87532023-10-011411810.1186/s13100-023-00303-8Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglementNikola A. Mizgier0Charlie E. Jones1Anthony V. Furano2Laboratory of Cellular and Molecular Biology, NIDDK, National Institutes of HealthLaboratory of Cellular and Molecular Biology, NIDDK, National Institutes of HealthLaboratory of Cellular and Molecular Biology, NIDDK, National Institutes of HealthAbstract L1 (LINE1) non-LTR retrotransposons are ubiquitous genomic parasites and the dominant transposable element in humans having generated about 40% of their genomic DNA during their ~ 100 million years (Myr) of activity in primates. L1 replicates in germ line cells and early embryos, causing genetic diversity and defects, but can be active in some somatic stem cells, tumors and during aging. L1 encodes two proteins essential for retrotransposition: ORF2p, a reverse transcriptase that contains an endonuclease domain, and ORF1p, a coiled coil mediated homo trimer, which functions as a nucleic acid chaperone. Both proteins contain highly conserved domains and preferentially bind their encoding transcript to form an L1 ribonucleoprotein (RNP), which mediates retrotransposition. However, the coiled coil has periodically undergone episodes of substantial amino acid replacement to the extent that a given L1 family can concurrently express multiple ORF1s that differ in the sequence of their coiled coils. Here we show that such distinct ORF1p sequences can become entangled forming heterotrimers when co-expressed from separate vectors and speculate on how coiled coil entanglement could affect coiled coil evolution.https://doi.org/10.1186/s13100-023-00303-8L1 retrotransposonL1 ORF1pCoiled coilsCoiled coil evolution
spellingShingle Nikola A. Mizgier
Charlie E. Jones
Anthony V. Furano
Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement
Mobile DNA
L1 retrotransposon
L1 ORF1p
Coiled coils
Coiled coil evolution
title Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement
title_full Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement
title_fullStr Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement
title_full_unstemmed Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement
title_short Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement
title_sort co expression of distinct l1 retrotransposon coiled coils can lead to their entanglement
topic L1 retrotransposon
L1 ORF1p
Coiled coils
Coiled coil evolution
url https://doi.org/10.1186/s13100-023-00303-8
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AT anthonyvfurano coexpressionofdistinctl1retrotransposoncoiledcoilscanleadtotheirentanglement