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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''KHDRBS3''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Interactions

KHDRBS3 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

SIAH1 E3 ubiquitin-protein ligase SIAH1 is an enzyme that in humans is encoded by the ''SIAH1'' gene. Function This gene encodes for a polypeptide structure that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligas ...

. 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 cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

tissue compared to the surrounding benign tissue. Expression of KHDRBS3 correlates with mpMRI signal measured through Likert score a system similar to

PI-RADS PI-RADS is an acronym for Prostate Imaging Reporting and Data System, defining standards of high quality clinical service for multi-parametric Magnetic Resonance Imaging (mpMRI), including image creation and reporting. History In 2007, the AdMeT ...

. While still under debate, mpMRI signal correlates with higher Gleason grade and tumour size, in addition to

histopathological Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...

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, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

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 c ...

''), 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 from ...

''), 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 media ...

''), troponin I3 (''

TNNI3 Troponin I, cardiac muscle is a protein that in humans is encoded by the ''TNNI3'' gene. It is a tissue-specific subtype of troponin I Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, wh ...

''), troponin T2 (''

TNNT2 Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the ''TNNT2'' gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle c ...

''), tropomyosin 1 (''

TPM1 Tropomyosin alpha-1 chain is a protein that in humans is encoded by the ''TPM1'' gene. This gene is a member of the tropomyosin (Tm) family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striate ...

''), tropomyosin 2 (''

TPM2 β-Tropomyosin, also known as tropomyosin beta chain is a protein that in humans is encoded by the ''TPM2'' gene. β-tropomyosin is striated muscle-specific coiled coil dimer that functions to stabilize actin filaments and regulate muscle contract ...

''), and titin (''

TTN ''ttn'' (''the total news'') was a 30 minute weekly Australian news program aimed at school-aged (9- to 14-year-old) children produced and broadcast by Network Ten from 2004 to 2008. It presented current issues and events in a way that could b ...

)''. 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 RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns (non-coding regions of RNA) and ''splicing'' ba ...

of the sacromere protein titin (

), 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., gene. ...

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's lab in Kyoto, Japan, who showed in ...

-derived cardiomyocytes (iPSC-CMs) increased Ca²⁺ transient amplitude and resulted in an increase of F_max.

Interactions

Clinical significance

Function

References

Further reading