TARDBP : TAR DNA binding protein

Description

The TARDBP (TAR DNA binding protein) is a protein-coding gene located on chromosome 1.

The TARDBP gene provides instructions for making a protein called transactive response DNA binding protein 43 kDa (TDP-43). This protein is found within the cell nucleus in most tissues and is involved in many of the steps of protein production. The TDP-43 protein attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. This protein can also bind to RNA, a chemical cousin of DNA, to ensure the RNA's stability. The TDP-43 protein is involved in processing molecules called messenger RNA (mRNA), which serve as the genetic blueprints for making proteins. By cutting and rearranging mRNA molecules in different ways, the TDP-43 protein controls the production of different versions of certain proteins. This process is known as alternative splicing. The TDP-43 protein can influence various functions of a cell by regulating protein production. The TARDBP gene is particularly active (expressed) during early development before birth when new tissues are forming. Many of the proteins whose production is influenced by the TDP-43 protein are involved in nervous system and organ development.

TARDBP, also known as TDP-43, is an RNA-binding protein crucial for various stages of RNA biogenesis and processing. Its two RNA recognition motifs (RRM1 and RRM2) enable it to bind preferentially to GU-repeats found within long introns and the 3'UTR of mRNAs. This binding influences the splicing of numerous non-coding and protein-coding RNAs, including those involved in neuronal survival and encoding proteins relevant to neurodegenerative diseases. Additionally, TARDBP contributes to maintaining mitochondrial homeostasis by regulating mitochondrial transcript processing and regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase to mRNA 3'UTR, leading to poly(A) tail deadenylation and shortening. In response to oxidative stress, TARDBP associates with stalled ribosomes localized to stress granules (SGs), promoting cell survival. Furthermore, it participates in skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins. TARDBP also plays a role in maintaining circadian clock periodicity by stabilizing CRY1 and CRY2 proteins in a FBXL3-dependent manner. It negatively regulates the expression of CDK6 and regulates the expression of HDAC6, ATG7, and VCP in a PPIA/CYPA-dependent manner.

TARDBP is also known as ALS10, TDP-43.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing