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Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5

ABSTRACT: Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5

PROVIDER: PRJNA1139208 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29932348.fastq.gz	Fastqsanger.gz
	SRR29932349.fastq.gz	Fastqsanger.gz
	SRR29932350.fastq.gz	Fastqsanger.gz
	SRR29932351.fastq.gz	Fastqsanger.gz
	SRR29932352.fastq.gz	Fastqsanger.gz

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Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5 [ChIP-Seq]

Project description:Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5 [ChIP-Seq]

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Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5

Project description:MicroRNAs (miRNAs) are small non-coding RNAs that play crucial roles in post-transcriptional gene regulation. Poly(A) RNA polymerase D5 (PAPD5) catalyzes the addition of adenosine to the 3′ end of miRNAs. In this study, we demonstrated that the Yin Yang 1 protein, a transcriptional repressor of PAPD5, was recruited to both RNA foci and protein aggregates, resulting in an upregulation of PAPD5 expression in Huntington’s disease (HD). Additionally, we identified a subset of PAPD5-regulated miRNAs with increased adenylation and reduced expression in our disease model. We focused on miR-7-5p and found that its reduction caused the activation of the TAB2-mediated TAK1–MKK4–JNK pro-apoptotic pathway. This pathway was also activated in induced pluripotent stem cell-derived striatal neurons and post-mortem striatal tissues isolated from HD patients. In addition, we discovered that a small molecule PAPD5 inhibitor, BCH001, could mitigate cell death and neurodegeneration in our disease models. This study highlights the importance of PAPD5-mediated miRNA dysfunction in HD pathogenesis and suggests a potential therapeutic direction for the disease.

2024-08-01 | GSE272903 | GEO

Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5 [ChIP-Seq]

2024-08-01 | GSE273082 | GEO

PAPD5, a noncanonical poly(A) polymerase with an unusual RNA-binding motif [PAR-CLIP]

2012-04-03 | GSE36987 | GEO

PAPD5, a noncanonical poly(A) polymerase with an unusual RNA-binding motif [PAR-CLIP]

Project description:PAPD5 is one of the seven members of non-canonical poly(A) polymerases in human cells. There are previous reports about polyadenylation dependent degradation of pre-ribosomal RNAs and uridylation dependent degradation of histone mRNAs in vivo. In this study, we observed polyadenylation but not polyuridylation activity of PAPD5 with in vitro assays. We aimed to get genome-wide targets of PAPD5 and used PAR-CLIP and deep sequencing for this purpose. Recombinant version of PAPD5 is expressed in HEK293 human cell lines and its genome wide targets are obtained with PAR-CLIP and deep sequencing as two replicate experiments. The short reads in the deep sequencing libraries of PAPD5 replicates and an unrelated protein to polymerization from a previous study, IGF2BP1, are aligned to the hg18 human genome assembly. The biological variance of the read counts in overlapping 100-nucleotide-long-windows is estimated between the PAPD5 replicates and further used in the differential expression estimations between the 100-nucleotide windows in PAPD5 replicates and IGF2BP1. The top differentially expressed windows in PAPD5 and IGF2BP1 are further annotated using gene and repeat tracks from UCSC.

2012-04-02 | E-GEOD-36987 | biostudies-arrayexpress

The non-canonical poly(A) polymerase FAM46C promotes erythropoiesis

Project description:The non-canonical poly(A) polymerase FAM46C promotes erythropoiesis

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The non-canonical poly(A) polymerase FAM46C promotes erythropoiesis [ADAR_APOBEC]

Project description:The non-canonical poly(A) polymerase FAM46C promotes erythropoiesis [ADAR_APOBEC]

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The non-canonical poly(A) polymerase FAM46C promotes erythropoiesis [RIP]

Project description:The non-canonical poly(A) polymerase FAM46C promotes erythropoiesis [RIP]

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The non-canonical poly(A) polymerase FAM46C promotes erythropoiesis [CUT&RUN]

Project description:The non-canonical poly(A) polymerase FAM46C promotes erythropoiesis [CUT&RUN]