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Featured Article - September 2026: New RNA synthesis routes

Featured Article - September 2026: New RNA synthesis routes

"Primer- and template- independent RNA polymerization by terminal nucleotidyltransferase TENT4B" by Nagpal et al. (Nucleic Acids Research, Sep 23, 2026) is our featured scientific article for September.

RNA Polymerases normally need something to work with: a template that determines the sequence of the newly synthesized RNA, or an existing RNA molecule that can be extended. Terminal nucleotidyltransferases (TENTs) belong to the latter group and add nucleotides to the ends of existing RNA molecules. TENT4B is one of these enzymes and is involved in the regulation and processing of several cellular and viral RNAs.

But while studying TENT4B, Nagpal and colleagues noticed something unexpected: the enzyme consumed ATP even when no RNA substrate was present. Following up on this observation, they found that recombinant TENT4B can start RNA synthesis directly from free nucleotides – without either a primer or a template. With ATP, the enzyme generated RNA molecules thousands of nucleotides long. GTP could also be used but produced much shorter, self-limiting RNA chains. Even the purine diphosphates ADP and GDP could serve as substrates under the test conditions.

Why does this matter?

  • A new polymerase activity: TENT4B provides the first definitive evidence of primer- and template-independent RNA synthesis by a eukaryotic polymerase.
  • Unexpected substrate flexibility: TENT4B can use different purine nucleotides to generate RNA, with surprisingly different product outcomes depending on the substrate.
  • Potential for RNA biotechnology: Engineered TENT4B could offer a new route towards enzymatic RNA synthesis without a template or initiating oligonucleotides.

Want to contribute with your own research in this field?

Here are the details of some of the nucleotides used in this study to investigate the unusual substrate flexibility of TENT4B:
Product Cat. No. Amount Price
ADP - solid NU-1198-1G 1 g 101,00 €
NU-1198-5G 5 g 377,80 €
γ-(6-Aminohexyl)-ATP-Cy5 NU-833-CY5 160 µl (1 mM) 1.207,70 €
γ-(6-Aminohexyl)-GTP-Cy5 NU-834-CY5 160 µl (1 mM) 1.207,70 €
Yeast Poly(A) Polymerase RNT-006-S 30000 units 212,20 €
RNT-006-L 3 x 30000 units 572,90 €

[1] Nagpal et al. (2026) Primer- and template- independent RNA polymerization by terminal nucleotidyltransferase TENT4B Nucleic Acids Research, https://doi.org/10.1093/nar/gkag864

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