A conserved role for the ESCRT membrane budding complex in LINE retrotransposition

Autor: Ivana Celic, Irena Martirosyan, Jeffrey S. Han, Chun Dong, Axel V. Horn
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Cell Membranes
Cultured tumor cells
Retrotransposon
Biochemistry
Small interfering RNAs
Genetics (clinical)
Ribonucleoprotein
Genetics
Membrane budding
Complementary DNA
Transport protein
Cell biology
Precipitation Techniques
ESCRT complex
Nucleic acids
Protein Transport
Ribonucleoproteins
Cell lines
Cellular Structures and Organelles
Biological cultures
Protein Binding
Research Article
lcsh:QH426-470
Endosome
Forms of DNA
Saccharomyces cerevisiae
Biology
Research and Analysis Methods
ESCRT
03 medical and health sciences
Nuclear Membrane
Humans
Immunoprecipitation
HeLa cells
Non-coding RNA
Molecular Biology Techniques
Molecular Biology
Ecology
Evolution
Behavior and Systematics
Cell Nucleus
Endosomal Sorting Complexes Required for Transport
Cell Membrane
Biology and Life Sciences
Proteins
DNA
Cell Biology
biology.organism_classification
Cell cultures
Gene regulation
lcsh:Genetics
030104 developmental biology
Long Interspersed Nucleotide Elements
RNA
Gene expression
Cloning
Zdroj: PLoS Genetics
PLoS Genetics, Vol 13, Iss 6, p e1006837 (2017)
ISSN: 1553-7404
Popis: Long interspersed nuclear element-1s (LINE-1s, or L1s) are an active family of retrotransposable elements that continue to mutate mammalian genomes. Despite the large contribution of L1 to mammalian genome evolution, we do not know where active L1 particles (particles in the process of retrotransposition) are located in the cell, or how they move towards the nucleus, the site of L1 reverse transcription. Using a yeast model of LINE retrotransposition, we identified ESCRT (endosomal sorting complex required for transport) as a critical complex for LINE retrotransposition, and verified that this interaction is conserved for human L1. ESCRT interacts with L1 via a late domain motif, and this interaction facilitates L1 replication. Loss of the L1/ESCRT interaction does not impair RNP formation or enzymatic activity, but leads to loss of retrotransposition and reduced L1 endonuclease activity in the nucleus. This study highlights the importance of the ESCRT complex in the L1 life cycle and suggests an unusual mode for L1 RNP trafficking.
Author summary Long interspersed nuclear elements (LINEs) are a class of retrotransposable elements that mutate mammalian genomes. LINEs have been highly successful in the human genome, multiplying to over 800,000 copies. The LINE-encoded replication machinery is also used by other retrotransposons, and in total, has been responsible for the generation of over 1/3 of human DNA sequence. To replicate, a LINE mRNA forms a ribonucleoprotein particle (RNP) with its proteins. This RNP eventually enters the nucleus to integrate a cDNA copy of itself into chromosomes. The events between RNP formation and successful integration are difficult to study and largely unknown. Here we show that the ESCRT complex plays a conserved role in LINE retrotransposition in both yeast and humans. ESCRT is a membrane budding complex involved in cellular trafficking and membrane budding/fusion. Our results imply that membranes play an integral part of LINE replication, and ESCRT may be required for RNP trafficking towards the nucleus.
Databáze: OpenAIRE
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