Aberrant interaction of FUS with the U1 snRNA provides a molecular mechanism of FUS induced amyotrophic lateral sclerosis

Jutzi, Daniel; Campagne, Sébastien; Schmidt, Ralf; Reber, Stefan; Mechtersheimer, Jonas; Gypas, Foivos; Schweingruber, Christoph; Colombo, Martino; Schroetter, Christine von; Loughlin, Fionna E.; Devoy, Anny; Hedlund, Eva; Zavolan, Mihaela; Allain, Frédéric H.‐T.; Ruepp, Marc‐David

doi:10.1038/s41467-020-20191-3

Cited by 56 publications

(82 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CLIP has been adopted to detect methyl adenosine 6 (m6A) modification sites [ 48 , 49 ] as well as secondary structure sites [ 50 ]. Furthermore, the combined analysis of CLIP and mass spectroscopy has been used to determine the precise regions of a protein that contact RNA [ 51 , 52 , 53 ].…”

Section: General Methods To Identify Protein–rna Interaction Sites In Rnamentioning

confidence: 99%

Rapidly Growing Protein-Centric Technologies to Extensively Identify Protein–RNA Interactions: Application to the Analysis of Co-Transcriptional RNA Processing

Matsubara

Kawachi

Ohno

2021

IJMS

View full text Add to dashboard Cite

During mRNA transcription, diverse RNA-binding proteins (RBPs) are recruited to RNA polymerase II (RNAP II) transcription machinery. These RBPs bind to distinct sites of nascent RNA to co-transcriptionally operate mRNA processing. Recent studies have revealed a close relationship between transcription and co-transcriptional RNA processing, where one affects the other’s activity, indicating an essential role of protein–RNA interactions for the fine-tuning of mRNA production. Owing to their limited amount in cells, the detection of protein–RNA interactions specifically assembled on the transcribing RNAP II machinery still remains challenging. Currently, cross-linking and immunoprecipitation (CLIP) has become a standard method to detect in vivo protein–RNA interactions, although it requires a large amount of input materials. Several improved methods, such as infrared-CLIP (irCLIP), enhanced CLIP (eCLIP), and target RNA immunoprecipitation (tRIP), have shown remarkable enhancements in the detection efficiency. Furthermore, the utilization of an RNA editing mechanism or proximity labeling strategy has achieved the detection of faint protein–RNA interactions in cells without depending on crosslinking. This review aims to explore various methods being developed to detect endogenous protein–RNA interaction sites and discusses how they may be applied to the analysis of co-transcriptional RNA processing.

show abstract

Section: General Methods To Identify Protein–rna Interaction Sites In Rnamentioning

confidence: 99%

Rapidly Growing Protein-Centric Technologies to Extensively Identify Protein–RNA Interactions: Application to the Analysis of Co-Transcriptional RNA Processing

Matsubara

Kawachi

Ohno

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…RBPs interact with a diverse range of RNAs. As a single RNA binding protein can bind to many thousands of RNA targets, a disturbance in one or more of these RBPs potentially has a broad and diverse impact on RNA metabolism [ 82 , 83 , 84 ]. Deregulated RNA metabolism has been described at many levels in ALS, including intron retention [ 14 ] and skipping of constitutive exons [ 85 , 86 ].…”

Section: Mechanisms Of Rna Binding Protein Dysfunction In Alsmentioning

confidence: 99%

The Interplay of RNA Binding Proteins, Oxidative Stress and Mitochondrial Dysfunction in ALS

2021

View full text Add to dashboard Cite

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. In this review, we highlight the mechanistic interplay between RNA binding protein dysregulation, oxidative stress and mitochondrial dysfunction in ALS. We also discuss different potential therapeutic strategies targeting these pathways.

show abstract

“…For example, while over-expression of progerin in iPSC-mDA neurons induced rapid ageing in vitro, the maturity of the resulting cells was not investigated, raising the possibility that ageing had been induced in foetal-like neurons, possibly contributing to the lack of some agerelated features in this model [50]. Similarly, the issue of developmental immaturity of hiPSC progeny is raised in a recent study investigating ALS, which is overcome by inducing cellular stress, targeting immaturity with a solution more suitable to cellular rejuvenation [66].…”

Section: Translational Insightmentioning

confidence: 99%

Modelling late-onset diseases with induced pluripotent stem cells: a matter of time management

Cossins¹,

Fairchild²

2021

Cell Gene Therapy Insights

View full text Add to dashboard Cite

The advent of induced pluripotent stem cells (iPSC) has revolutionised in vitro modelling of many intractable human diseases. By deriving iPSC from individuals with progressive disease, it has been possible to capture disease-associated genes and study their impact on the downstream function of terminally-differentiated cell types. Nevertheless, late onset diseases pose particular challenges for disease modelling given the protracted time frame over which they normally develop. Such practical issues are accentuated by the propensity for iPSC to produce cell types of foetal origin rather than their adult counterparts and by the rejuvenation of the resulting cells, thereby erasing any physiological evidence of ageing. Here we review progress in overcoming these issues and argue that achieving a combination of maturation and ageing will enable better recapitulation of all features of late-onset diseases.

show abstract

Aberrant interaction of FUS with the U1 snRNA provides a molecular mechanism of FUS induced amyotrophic lateral sclerosis

Cited by 56 publications

References 78 publications

Rapidly Growing Protein-Centric Technologies to Extensively Identify Protein–RNA Interactions: Application to the Analysis of Co-Transcriptional RNA Processing

Rapidly Growing Protein-Centric Technologies to Extensively Identify Protein–RNA Interactions: Application to the Analysis of Co-Transcriptional RNA Processing

The Interplay of RNA Binding Proteins, Oxidative Stress and Mitochondrial Dysfunction in ALS

Modelling late-onset diseases with induced pluripotent stem cells: a matter of time management

Contact Info

Product

Resources

About