RGD Reference Report - TDP-43 localizes in mRNA transcription and processing sites in mammalian neurons. - Rat Genome Database

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TDP-43 localizes in mRNA transcription and processing sites in mammalian neurons.

Authors: Casafont, I  Bengoechea, R  Tapia, O  Berciano, MT  Lafarga, M 
Citation: Casafont I, etal., J Struct Biol. 2009 Sep;167(3):235-41. Epub 2009 Jun 16.
RGD ID: 5687141
Pubmed: PMID:19539030   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jsb.2009.06.006   (Journal Full-text)

TDP-43 is a RNA/DNA-binding protein structurally related to nuclear hnRNP proteins. Previous biochemical studies have shown that this nuclear protein plays a role in the regulation of gene transcription, alternative splicing and mRNA stability. Despite the ubiquitous distribution of TDP-43, the growing list of TDP-43 proteinopathies is primarily associated with neurodegenerative disorders. Particularly, TDP-43 redistributes to the cytoplasm and forms pathological inclusions in amyotrophic lateral sclerosis and several forms of sporadic and familiar frontotemporal lobar degeneration. Here, we have studied the nuclear compartmentalization of TDP-43 in normal rat neurons by using light and electron microscopy immunocytochemistry with molecular markers for nuclear compartments, a transcription assay with 5'-fluorouridine, and in situ hybridization for telomeric DNA. TDP-43 is concentrated in euchromatin domains, specifically in perichromatin fibrils, nuclear sites of transcription and cotranscriptional splicing. In these structures, TDP-43 colocalizes with 5'-fluorouridine incorporation sites into nascent pre-mRNA. TDP-43 is absent in transcriptionally silent centromeric and telomeric heterochromatin, as well as in the Cajal body, a transcription free nuclear compartment. Furthermore, a weak TDP-43 immunolabeling is found in nuclear speckles of splicing factors. The specific localization of TDP-43 in active sites of transcription and cotranscriptional splicing is consistent with biochemical data indicating a role of TDP-43 in the regulation of transcription and alternative splicing.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
interchromatin granule  IDA 5687141 RGD 
nuclear speck  IDA 5687141 RGD 
perichromatin fibrils  IDA 5687141 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tardbp  (TAR DNA binding protein)


Additional Information