Splicing events and transcriptome changes upon TDP-43 and FUS knock-down in human neuroblastoma cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE67027 | GEO | 2018/03/18
REPOSITORIES: GEO
Similar Datasets
Project description:We performed RNA immunoprecipitation (IP) and microarray (RIP-chip) analyses to identify and compare the biological mRNA targets of two RNA-binding protein (RBP), TDP-43 and FUS, associated to cytoplasmic ribonucleoprotein (RNP) complexes of motoneuronal NSC34 cells with the final aim to unravel their role in mRNA transport, stability, and translation in neuronal cells. To identify the transcripts contained and bound in the isolated RNP complexes, a chip analysis was performed using the recovered mRNAs from triplicate experimantal RIP samples (TDP-43-IP samples, the FUS-IP samples and the control IgG-IP sample).
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Project description:FUS/TLS and TDP-43 are RNA/DNA-binding proteins integrally involved in amyotrophic lateral sclerosis (ALS) and frontal temporal dementia. FUS/TLS is shown to bind RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU binding motif. A characteristic sawtooth-like binding pattern is identified, supporting co-transcriptional deposition of FUS/TLS. Depletion of FUS/TLS from the adult nervous system is shown to alter levels or splicing of >970 mRNAs, most of which are distinct from the RNAs whose maturation is dependent on TDP-43. Nonetheless, only 55 RNAs are reduced upon depletion of either TDP-43 or FUS/TLS from mouse brain and human neurons differentiated from pluripotent stem cells, including mRNAs transcribed from genes with exceptionally long introns and that encode proteins essential for neuronal integrity. A subset of these is significantly lowered in FUS/TLSR521G and TDP-43G298S mutant fibroblasts and in TDP-43 aggregate-containing motor neurons in sporadic ALS, evidence pointing to a common loss-of-function pathway as one component underlying motor neuron death from misregulation of TDP-43 or FUS/TLS. Microarray of Fus/Tls in 8 week mouse brain
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Project description:This SuperSeries is composed of the following subset Series: GSE40649: Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (microarray) GSE40651: Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (CLIP-Seq) GSE40652: Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (RNA-Seq) Refer to individual Series
2012-09-30 | E-GEOD-40653 | biostudies-arrayexpress
Project description:FUS/TLS and TDP-43 are RNA/DNA-binding proteins integrally involved in amyotrophic lateral sclerosis (ALS) and frontal temporal dementia. FUS/TLS is shown to bind RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU binding motif. A characteristic sawtooth-like binding pattern is identified, supporting co-transcriptional deposition of FUS/TLS. Depletion of FUS/TLS from the adult nervous system is shown to alter levels or splicing of >970 mRNAs, most of which are distinct from the RNAs whose maturation is dependent on TDP-43. Nonetheless, only 55 RNAs are reduced upon depletion of either TDP-43 or FUS/TLS from mouse brain and human neurons differentiated from pluripotent stem cells, including mRNAs transcribed from genes with exceptionally long introns and that encode proteins essential for neuronal integrity. A subset of these is significantly lowered in FUS/TLSR521G and TDP-43G298S mutant fibroblasts and in TDP-43 aggregate-containing motor neurons in sporadic ALS, evidence pointing to a common loss-of-function pathway as one component underlying motor neuron death from misregulation of TDP-43 or FUS/TLS. CLIP of Fus/Tls in 8 week mouse brain and adult human brain
2012-09-30 | E-GEOD-40651 | biostudies-arrayexpress
Project description:FUS/TLS and TDP-43 are RNA/DNA-binding proteins integrally involved in amyotrophic lateral sclerosis (ALS) and frontal temporal dementia. FUS/TLS is shown to bind RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU binding motif. A characteristic sawtooth-like binding pattern is identified, supporting co-transcriptional deposition of FUS/TLS. Depletion of FUS/TLS from the adult nervous system is shown to alter levels or splicing of >970 mRNAs, most of which are distinct from the RNAs whose maturation is dependent on TDP-43. Nonetheless, only 55 RNAs are reduced upon depletion of either TDP-43 or FUS/TLS from mouse brain and human neurons differentiated from pluripotent stem cells, including mRNAs transcribed from genes with exceptionally long introns and that encode proteins essential for neuronal integrity. A subset of these is significantly lowered in FUS/TLSR521G and TDP-43G298S mutant fibroblasts and in TDP-43 aggregate-containing motor neurons in sporadic ALS, evidence pointing to a common loss-of-function pathway as one component underlying motor neuron death from misregulation of TDP-43 or FUS/TLS. RNA-Seq of Fus/Tls in 8 week mouse brain
2012-09-30 | E-GEOD-40652 | biostudies-arrayexpress
Project description:We performed RNA immunoprecipitation (IP) and microarray (RIP-chip) analyses to identify and compare the biological mRNA targets of two RNA-binding proteins (RBP), TDP-43 and FUS, associated to cytoplasmic ribonucleoprotein (RNP) complexes of motoneuronal NSC-34 cells with the final aim to unravel their role in mRNA transport, stability, and translation in neuronal cells.
2011-10-22 | GSE33159 | GEO
Project description:FUS/TLS and TDP-43 are RNA/DNA-binding proteins integrally involved in amyotrophic lateral sclerosis (ALS) and frontal temporal dementia. FUS/TLS is shown to bind RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU binding motif. A characteristic sawtooth-like binding pattern is identified, supporting co-transcriptional deposition of FUS/TLS. Depletion of FUS/TLS from the adult nervous system is shown to alter levels or splicing of >970 mRNAs, most of which are distinct from the RNAs whose maturation is dependent on TDP-43. Nonetheless, only 55 RNAs are reduced upon depletion of either TDP-43 or FUS/TLS from mouse brain and human neurons differentiated from pluripotent stem cells, including mRNAs transcribed from genes with exceptionally long introns and that encode proteins essential for neuronal integrity. A subset of these is significantly lowered in FUS/TLSR521G and TDP-43G298S mutant fibroblasts and in TDP-43 aggregate-containing motor neurons in sporadic ALS, evidence pointing to a common loss-of-function pathway as one component underlying motor neuron death from misregulation of TDP-43 or FUS/TLS.
2012-09-30 | GSE40649 | GEO
Project description:FUS/TLS and TDP-43 are RNA/DNA-binding proteins integrally involved in amyotrophic lateral sclerosis (ALS) and frontal temporal dementia. FUS/TLS is shown to bind RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU binding motif. A characteristic sawtooth-like binding pattern is identified, supporting co-transcriptional deposition of FUS/TLS. Depletion of FUS/TLS from the adult nervous system is shown to alter levels or splicing of >970 mRNAs, most of which are distinct from the RNAs whose maturation is dependent on TDP-43. Nonetheless, only 55 RNAs are reduced upon depletion of either TDP-43 or FUS/TLS from mouse brain and human neurons differentiated from pluripotent stem cells, including mRNAs transcribed from genes with exceptionally long introns and that encode proteins essential for neuronal integrity. A subset of these is significantly lowered in FUS/TLSR521G and TDP-43G298S mutant fibroblasts and in TDP-43 aggregate-containing motor neurons in sporadic ALS, evidence pointing to a common loss-of-function pathway as one component underlying motor neuron death from misregulation of TDP-43 or FUS/TLS.
2012-09-30 | GSE40652 | GEO
Project description:FUS/TLS and TDP-43 are RNA/DNA-binding proteins integrally involved in amyotrophic lateral sclerosis (ALS) and frontal temporal dementia. FUS/TLS is shown to bind RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU binding motif. A characteristic sawtooth-like binding pattern is identified, supporting co-transcriptional deposition of FUS/TLS. Depletion of FUS/TLS from the adult nervous system is shown to alter levels or splicing of >970 mRNAs, most of which are distinct from the RNAs whose maturation is dependent on TDP-43. Nonetheless, only 55 RNAs are reduced upon depletion of either TDP-43 or FUS/TLS from mouse brain and human neurons differentiated from pluripotent stem cells, including mRNAs transcribed from genes with exceptionally long introns and that encode proteins essential for neuronal integrity. A subset of these is significantly lowered in FUS/TLSR521G and TDP-43G298S mutant fibroblasts and in TDP-43 aggregate-containing motor neurons in sporadic ALS, evidence pointing to a common loss-of-function pathway as one component underlying motor neuron death from misregulation of TDP-43 or FUS/TLS.
2012-09-30 | GSE40651 | GEO
Project description:TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3â untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease. RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns This Series represents array sample(s).
2016-07-05 | E-GEOD-77699 | biostudies-arrayexpress