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Terminal nucleotidyltransferase 5B (TENT5B)

Target
TENT5B
Molecular classification
Enzyme (Non-canonical poly(A) polymerase / nucleotidyltransferase), Other: Catalytic protein with a prokaryotic-like structure
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Overview

Terminal nucleotidyltransferase 5B (TENT5B) is a human enzyme encoded by the *TENT5B* gene, previously known as *FAM46B*. It functions as a non-canonical poly(A) polymerase, catalyzing the addition of adenosine to mRNA poly(A) tails, and thus regulates mRNA stability and translation. TENT5B contains a larger N-terminal catalytic domain compared to other eukaryotic poly(A) polymerases and is structurally similar to prokaryotic PAP/CCA-adding enzymes. It is localized to both cytoplasm and nucleus and is highly expressed in human pre-implantation embryos and pluripotent stem cells, but is sharply down-regulated following differentiation. TENT5B is essential for the maintenance of protein synthesis and viability in embryonic stem cells, with knockout causing apoptosis and lethality. Recent studies highlight its critical role in gametogenesis (oogenesis), where its loss leads to infertility, particularly in mouse models[1][2][3][5][8][11].

Other names
TENT5BFAM46BFamily with sequence similarity 46 member BNon-canonical poly(A) polymerase FAM46BMGC16491Putative nucleotidyltransferase FAM46BProtein FAM46B
02

Biological functions

Poly(A) RNA polymerase activity (adds adenosine to mRNA poly(A) tails)Negative regulation of apoptotic processNegative regulation of cell population proliferationPositive regulation of translationMaintenance of mRNA stability and translational efficiencyEssential for embryonic stem cell viabilityRegulation of gametogenesis (oogenesis and potentially spermatogenesis)
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Disease associations

Developmental disorders (knockout is lethal in embryonic stem cells)Infertility (mutations in mouse models cause infertility and oocyte degeneration)Other: Potential role in cancer and cell cycle, but not yet definitively established
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Safety considerations

Knockout lethality: Complete loss of function is lethal to embryonic stem cells; thus, therapeutic inhibition might cause profound developmental toxicityInfertility: Loss of TENT5B (and especially combined loss with TENT5C) in mice leads to oocyte degeneration and infertility
05

Biomarkers

Embryonic stem cell viability marker (knockout results in lethality)

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