TDP-43
TDP-43 (TAR DNA-binding protein 43, encoded by TARDBP and also known as ALS10) is an RNA-binding protein involved in several steps of RNA biogenesis and processing. It binds GU-repeat RNA through two RNA recognition motifs and regulates splicing, mRNA stability and stress responses. Browse Assay Genie's current range of TDP-43 research reagents below, or read on for the biology behind the target.
TDP-43 is an RNA-binding protein that acts at multiple points in RNA biogenesis and processing. Through its two RNA recognition motifs, RRM1 and RRM2, it preferentially binds GU-repeats on RNA molecules, mainly within long introns and in the 3'UTR of mRNAs. From these sites it regulates the splicing of many non-coding and protein-coding RNAs, including transcripts for proteins involved in neuronal survival and for proteins relevant to neurodegenerative diseases.
TDP-43 also influences RNA fate beyond splicing. It regulates mRNA stability by recruiting the CNOT7/CAF1 deadenylase to the 3'UTR, which leads to poly(A) tail deadenylation and shortening. It helps maintain mitochondrial homeostasis by regulating the processing of mitochondrial transcripts. In response to oxidative insult, it associates with stalled ribosomes in stress granules and contributes to cell survival. In skeletal muscle, it forms cytoplasmic myo-granules and binds mRNAs encoding sarcomeric proteins, supporting muscle formation and regeneration. It further stabilises CRY1 and CRY2 in an FBXL3-dependent manner to maintain circadian clock periodicity, negatively regulates CDK6 expression, and regulates HDAC6, ATG7 and VCP expression in a PPIA/CYPA-dependent manner.
The TARDBP gene, a member of the RNA binding motif containing group, takes its name from the TAR DNA element of HIV-1. NCBI describes the encoded protein as a transcriptional repressor that binds chromosomally integrated TAR DNA and represses HIV-1 transcription, and as a regulator of alternative splicing of the CFTR gene. A similar pseudogene is present on chromosome 20. The alias ALS10 is also used for this gene. The mouse ortholog is Tardbp.
TDP-43 regulates splicing of RNAs encoding proteins involved in neuronal survival and in neurodegenerative disease, making it central to studies of neuronal RNA metabolism.
TDP-43 binds GU-repeat motifs in long introns and 3'UTRs, providing a model for studying splicing control and mRNA stability via CNOT7/CAF1.
Under oxidative insult TDP-43 associates with stalled ribosomes in stress granules and contributes to cell survival.
TDP-43 forms myo-granules in skeletal muscle regeneration and stabilises CRY1 and CRY2 to maintain circadian clock periodicity.
TDP-43 is an RNA-binding protein that binds GU-repeat RNA and regulates splicing, mRNA stability and the processing of mitochondrial transcripts. It also associates with stress granules during oxidative stress, contributes to muscle regeneration and supports circadian clock periodicity by stabilising CRY1 and CRY2.
The protein is named TAR DNA-binding protein 43 and the gene symbol is TARDBP, with the full HGNC name TAR DNA binding protein. ALS10 is a listed alias. The name refers to the HIV-1 TAR DNA element, which the protein binds to repress HIV-1 transcription.
A mouse ortholog, Tardbp, is recorded for the human TARDBP gene. A similar pseudogene is also present on human chromosome 20. Researchers working in other species should check the datasheet of any product for its validated reactivity.
Splicing targets, circadian regulators and autophagy-related proteins linked to TDP-43 function.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13148; product specifications from Assay Genie datasheets.