TY - JOUR
T1 - Retroelement-derived RNA and its role in the brain
AU - Evans, Taylor A.
AU - Erwin, Jennifer Ann
N1 - Funding Information:
JAE is supported by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation and Collaborative Center for X-Linked Dystonia Parkinsonism and the MGH Collaborative Center for X-Linked Dystonia- Parkinsonism.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2021/6
Y1 - 2021/6
N2 - Comprising ~40% of the human genome, retroelements are mobile genetic elements which are transcribed into RNA, then reverse-transcribed into DNA and inserted into a new site in the genome. Retroelements are referred to as “genetic parasites”, residing among host genes and relying on host machinery for transcription and evolutionary propagation. The healthy brain has the highest expression of retroelement-derived sequences compared to other somatic tissue, which leads to the question: how does retroelement-derived RNA influence human traits and cellular states? While the functional importance of upregulating retroelement expression in the brain is an active area of research, RNA species derived from retroelements influence both self- and host gene expression by contributing to chromatin remodeling, alternative splicing, somatic mosaicism and translational repression. Here, we review the emerging evidence that the functional importance of RNA derived from retroelements is multifaceted. Retroelements can influence organismal states through the seeding of epigenetic states in chromatin, the production of structured RNA and even catalytically active ribozymes, the generation of cytoplasmic ssDNA and RNA/DNA hybrids, the production of viral-like proteins, and the generation of somatic mutations. Comparative sequencing suggests that retroelements can contribute to intraspecies variation through these mechanisms to alter transcript identity and abundance. In humans, an increasing number of neurodevelopmental and neurodegenerative conditions are associated with dysregulated retroelements, including Aicardi-Goutieres syndrome (AGS), Rett syndrome (RTT), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), multiple sclerosis (MS), schizophrenia (SZ), and aging. Taken together, these concepts suggest a larger functional role for RNA derived from retroelements. This review aims to define retroelement-derived RNA, discuss how it impacts the mammalian genome, as well as summarize data supporting phenotypic consequences of this unique RNA subset in the brain.
AB - Comprising ~40% of the human genome, retroelements are mobile genetic elements which are transcribed into RNA, then reverse-transcribed into DNA and inserted into a new site in the genome. Retroelements are referred to as “genetic parasites”, residing among host genes and relying on host machinery for transcription and evolutionary propagation. The healthy brain has the highest expression of retroelement-derived sequences compared to other somatic tissue, which leads to the question: how does retroelement-derived RNA influence human traits and cellular states? While the functional importance of upregulating retroelement expression in the brain is an active area of research, RNA species derived from retroelements influence both self- and host gene expression by contributing to chromatin remodeling, alternative splicing, somatic mosaicism and translational repression. Here, we review the emerging evidence that the functional importance of RNA derived from retroelements is multifaceted. Retroelements can influence organismal states through the seeding of epigenetic states in chromatin, the production of structured RNA and even catalytically active ribozymes, the generation of cytoplasmic ssDNA and RNA/DNA hybrids, the production of viral-like proteins, and the generation of somatic mutations. Comparative sequencing suggests that retroelements can contribute to intraspecies variation through these mechanisms to alter transcript identity and abundance. In humans, an increasing number of neurodevelopmental and neurodegenerative conditions are associated with dysregulated retroelements, including Aicardi-Goutieres syndrome (AGS), Rett syndrome (RTT), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), multiple sclerosis (MS), schizophrenia (SZ), and aging. Taken together, these concepts suggest a larger functional role for RNA derived from retroelements. This review aims to define retroelement-derived RNA, discuss how it impacts the mammalian genome, as well as summarize data supporting phenotypic consequences of this unique RNA subset in the brain.
KW - HERV
KW - LINE-1
KW - Mobile DNA
KW - Neurodegenerative disease
KW - Neurodevelopment
KW - RNA biology
KW - Retrotransposons
KW - Rett syndrome
KW - SVA
KW - Somatic Mosaicism
KW - Transcriptomics
KW - Transposable element
KW - X-Linked Dystonia Parkinsonism
UR - http://www.scopus.com/inward/record.url?scp=85096620793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096620793&partnerID=8YFLogxK
U2 - 10.1016/j.semcdb.2020.11.001
DO - 10.1016/j.semcdb.2020.11.001
M3 - Review article
C2 - 33229216
AN - SCOPUS:85096620793
SN - 1084-9521
VL - 114
SP - 68
EP - 80
JO - Seminars in Cell and Developmental Biology
JF - Seminars in Cell and Developmental Biology
ER -