Dataset Information

Proteins that co-purify with tandem affinity-purified PRC5 in Trypanosoma brucei

ABSTRACT: The project was to determine the role of a trypanosomatid protein, termed PRC5, in pre-mRNA splicing. PRC5 has no homologs in model organisms but was recurrently co-purified with known splicing factors in Trypanosoma brucei. To determine interacting proteins, PRC5 was C-terminally TAP-tagged (we used the PTP tag) and tandem affinity-purified, and co-purifying proteins identified after separation by SDS-PAGE and in-gel trypsin digest by LC/MS/MS. Many of the enriched proteins were known splicing factors, and sucrose gradient sedimentation identified a complex of five subunits, termed PRP19-related complex or PRC.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Trypanosoma Brucei

TISSUE(S): Cell Suspension Culture

SUBMITTER: Arthur Gunzl

LAB HEAD: Arthur Gunzl

PROVIDER: PXD026239 | Pride | 2021-12-15

REPOSITORIES: Pride

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Publications

A distinct complex of PRP19-related and trypanosomatid-specific proteins is required for pre-mRNA splicing in trypanosomes.

Srivastava Ankita A Ambrósio Daniela L DL Tasak Monika M Gosavi Ujwala U Günzl Arthur A

Nucleic acids research 20211201 22

The pre-mRNA splicing factor PRP19 is recruited into the spliceosome after forming the PRP19/CDC5L complex in humans and the Nineteen complex in yeast. Additionally, 'PRP19-related' proteins enter the spliceosome individually or in pre-assemblies that differ in these systems. The protistan family Trypanosomatidae, which harbors parasites such as Trypanosoma brucei, diverged early during evolution from opisthokonts. While introns are rare in these organisms, spliced leader trans splicing is an ob ...[more]

PMID: 34850936

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Project description:Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder. To identify potential A2BP1-dependent differential splicing events in ASD brain, we performed high-throughput RNA sequencing (RNA-Seq) on three autism samples with significant downregulation of A2BP1 (average fold change by quantitative RT-PCR = 5.9) and three control samples with average A2BP1 levels. The list of potential A2BP1-depending differential splicing events in ASD is given in the Supplementary file linked at the foot of this record.

Dataset Information

Proteins that co-purify with tandem affinity-purified PRC5 in Trypanosoma brucei

Publications

A distinct complex of PRP19-related and trypanosomatid-specific proteins is required for pre-mRNA splicing in trypanosomes.

Similar Datasets

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