RNA targets of TDP-43 identified by UV-CLIP are deregulated in ALS
We have investigated the premise that abnormalities of TDP-43 in disease would be reflected by changes in processing of its target RNAs. To this end, we have firstly identified RNA targets of TDP-43 using UV-Cross-Linking and Immunoprecipitation (UV-CLIP) of SHSY5Y cells, a human neuroblastoma cell line.
Nuclear RNA binding regulates TDP-43 nuclear ... - ScienceDirect
2022年7月19日 · RNA crosslinking and immunoprecipitation-sequencing (CLIP-seq) studies show that TDP-43 preferentially binds GU-rich RNA motifs, particularly in introns (Polymenidou et al., 2011; Tollervey et al., 2011), consistent with its role in regulating alternative splicing and repression of cryptic exons (Ling et al., 2015).
TDP-43 condensation properties specify its RNA-binding and …
2021年8月10日 · ChimeraRBP-CLIP shows that the CTD-mediated homomultimeric contacts recruit the chimeric protein close to the RNA-binding regions of endogenous TDP-43. Three RNA features define the characteristics of binding-region condensates
Characterizing the RNA targets and position-dependent splicing ...
2011年2月27日 · Using individual nucleotide-resolution ultraviolet cross-linking and immunoprecipitation (iCLIP), we found that TDP-43 preferentially bound long clusters of UG-rich sequences in vivo. Analysis of...
Characterizing TDP-43 interaction with its RNA targets - PMC
Several cross-linking and immunoprecipitation (CLIP) and RNA immunoprecipitation-sequencing (RIP-seq) analyses have indicated that TDP-43 in vivo can also specifically bind loosely conserved UG/GU-rich repeats interspersed by other nucleotides. These sequences are predominantly localized within long introns and in the 3′UTR of various genes.
Characterising the RNA targets and position-dependent splicing ...
Using individual-nucleotide resolution UV-crosslinking and immunoprecipitation (iCLIP), we demonstrated that TDP-43 preferentially binds long clusters of UG-rich sequences in vivo. Analysis of TDP-43 RNA binding in FTLD-TDP brains revealed the greatest increases in binding to MALAT1 and NEAT1 non-coding RNAs.
Distinct and shared functions of ALS-associated proteins TDP
2016年7月5日 · To identify in vivo RNA substrates recognized by TAF15, we performed CLIP (crosslinking immunoprecipitation)-seq in whole-brain tissue from adult mice using a commercially available antibody that...
TDP-43，登顶Cell 的新热点蛋白 - 知乎 - 知乎专栏
2020 年 10 月 3 日，墨尔本大学的 Seth L. Masters 教授团队发表题为 「TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS」 的研究成果， 阐释了 TDP-43 通过在线粒体的累积，诱导线粒体 DNA 向细胞质释放，并进一步激活 cGAS/STING 信号通路，引起 NF-κB 和 I 型干扰素信号通路 的升高，进而引起神经细胞炎症和运动神经功能症状。 这一发现为使用 SITNG 抑制剂对渐冻症患者进行干预治疗提供了理论基础。 研究背景.
The cooperative binding of TDP-43 to GU-rich RNA repeats ... - eLife
2021年9月7日 · To understand through which molecular mechanisms TDP-43 targets pyrimidine-rich introns in cells as revealed by CLIP experiments, we considered whether a cooperative association of TDP-43 may take place in long GU-rich repeats to secure the binding of several TDP-43 proteins.
TDP‐43 regulates its mRNA levels through a negative feedback loop
TAR DNA‐binding protein (TDP‐43) is an evolutionarily conserved heterogeneous nuclear ribonucleoprotein (hnRNP) involved in RNA processing, whose abnormal cellular distribution and post‐translational modification are key markers of certain neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration.