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Cas9 interactions with host RNAs and transposable elements impair neurodevelopment

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161635 | GEO | 2022/12/31

REPOSITORIES: GEO

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Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (irCLIP-seq)

Project description:The CRISPR (clustered regulatory interspaced short palindromic repeats)/ Cas9 (CRISPR-associated protein 9) system-based precise genome editing has revolutionized biomedical studies. As the CRISPR/Cas9 system has been also recently considered to permanently cure genetic diseases via human germline genome editing, a careful risk assessment of this genome engineering tool is required in human early development. Here we perform comprehensive analysis to evaluate the potential impact of Cas9 in human early embryogenesis. We find that even in the absence of synthetic guide RNA, Cas9 can be still guided by endogenous RNAs, and cut the genome of human embryonic cells at low frequency, and the resulting DNA damage induces the intrinsic immune response. Moreover, Cas9 interferes with the spliceosome, and with the suppressor machinery (e.g. L1TD1, APOBEC3G and PIWIL4) of LINE-1 (L1) retrotransposition. Even the transient presence of Cas9 in human embryonic cells induces robust de novo L1 retrotransposition that exacerbates DNA damage, and results in compromised neurodevelopment. Besides the ethical issues, these inevitable and detrimental Cas9-associated impacts on human embryonic development raise such serious safety concerns as to question the clinical use of human germline genome editing.

2022-12-31 | GSE161632 | GEO

Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (RNA-seq)

2022-12-31 | GSE161634 | GEO

Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (CUT&Tag)

2022-12-31 | GSE161633 | GEO

Cas9 interactions with host RNAs and transposable elements impair neurodevelopment

Project description:Cas9 interactions with host RNAs and transposable elements impair neurodevelopment

| PRJNA678973 | ENA

Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (irCLIP-seq)

Project description:Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (irCLIP-seq)

| PRJNA678977 | ENA

Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (CUT&Tag)

Project description:Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (CUT&Tag)

| PRJNA678978 | ENA

Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (RNA-seq)

Project description:Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (RNA-seq)

| PRJNA678979 | ENA

Analysis of 3D interactions identifies candidate host genes that transposable elements potentially regulate

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-11-28 | GSE122977 | GEO

Transposable elements (TEs) contribute to stress-related long intergenic noncoding RNAs in Plants

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-01-22 | GSE92444 | GEO

Analysis of 3D genomic interactions identifies candidate host genes that transposable elements potentially regulate.

Project description:BackgroundThe organization of chromatin in the nucleus plays an essential role in gene regulation. About half of the mammalian genome comprises transposable elements. Given their repetitive nature, reads associated with these elements are generally discarded or randomly distributed among elements of the same type in genome-wide analyses. Thus, it is challenging to identify the activities and properties of individual transposons. As a result, we only have a partial understanding of how transposons contribute to chromatin folding and how they impact gene regulation.ResultsUsing PCR and Capture-based chromosome conformation capture (3C) approaches, collectively called 4Tran, we take advantage of the repetitive nature of transposons to capture interactions from multiple copies of endogenous retrovirus (ERVs) in the human and mouse genomes. With 4Tran-PCR, reads are selectively mapped to unique regions in the genome. This enables the identification of transposable element interaction profiles for individual ERV families and integration events specific to particular genomes. With this approach, we demonstrate that transposons engage in long-range intra-chromosomal interactions guided by the separation of chromosomes into A and B compartments as well as topologically associated domains (TADs). In contrast to 4Tran-PCR, Capture-4Tran can uniquely identify both ends of an interaction that involve retroviral repeat sequences, providing a powerful tool for uncovering the individual transposable element insertions that interact with and potentially regulate target genes.Conclusions4Tran provides new insight into the manner in which transposons contribute to chromosome architecture and identifies target genes that transposable elements can potentially control.

| S-EPMC6292174 | biostudies-literature

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