KH domain-containing, RNA-binding, signal transduction-associated protein 3 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''KHDRBS3''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Interactions
KHDRBS3 has been shown to
interact with
SIAH1.
KHDRBS3 interacts with splicing protein Sam68 and oncogene
metadherin in prostate cancer cells.
Clinical significance
KHDRBS3 (T-STAR) expression has been shown to be increased in
prostate cancer
Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...
tissue compared to the surrounding benign tissue.
Expression of KHDRBS3 correlates with
mpMRI signal measured through Likert score a system similar to
PI-RADS.
While still under debate, mpMRI signal correlates with higher
Gleason grade and tumour size, in addition to
histopathological
Histopathology (compound of three Greek language, Greek words: 'tissue', 'suffering', and ''-logy, -logia'' 'study of') is the light microscope, microscopic examination of Tissue (biology), tissue in order to study the manifestations of dis ...
features associated with clinically aggressive prostate cancer.
Expression of KHDRBS3 was increased in the failing human myocardium of
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood.
Although symptoms vary based on which side of the heart is affected, HF ...
patients, here KHDRBS3 protein interacted with several important mRNAs coding for sarcomere components, such as actin gamma 1 (''
ACTG1
Actin, cytoplasmic 2, or gamma-actin is a protein that in humans is encoded by the ''ACTG1'' gene. Gamma-actin is widely expressed in cellular cytoskeletons of many tissues; in adult striated muscle cells, gamma-actin is localized to Z-discs and ...
''), myosin light chain 2 (''
MYL2
Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2) also known as the regulatory light chain of myosin (RLC) is a protein that in humans is encoded by the ''MYL2'' gene. This cardiac ventricular RLC isoform is distinct fro ...
''), ryanodine receptor 2 (''
RYR2
Ryanodine receptor 2 (RYR2) is one of a class of ryanodine receptors and a protein found primarily in cardiac muscle. In humans, it is encoded by the ''RYR2'' gene. In the process of cardiac calcium-induced calcium release, RYR2 is the major med ...
''), troponin I3 (''
TNNI3
Troponin I, cardiac muscle is a protein that in humans is encoded by the ''TNNI3'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that ...
''), troponin T2 (''
TNNT2''), tropomyosin 1 (''
TPM1''), tropomyosin 2 (''
TPM2''), and titin (''
TTN)''.
In prostate cancer cell lines KHDRBS3 appears to be androgen regulated, with a reduction in mRNA expression occurring following addition of synthetic androgen
R1881 to cells.
Function
KHDRBS3 regulates the alternative
mRNA splicing of the
sacromere protein titin (
TTN), leading to
intron
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
retention. Overexpression of KHDRBS3 in
induced pluripotent stem cell
Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka and Kazutoshi Takahashi in Kyoto, Jap ...
-derived cardiomyocytes (iPSC-CMs) increased Ca
2+ transient amplitude and resulted in an increase of F
max.
References
Further reading
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