Structure–Function Relationships of Cid1 Poly(U) Polymerase: Catalysis, Substrate Recognition, Engineering, and Applications
- 1Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru 81310, Malaysia
- 2School of Life Sciences, Henan Institute of Science and Technology, Xinxiang 453003, China
Abstract
RNA 3′-end modification is an important regulatory mechanism that influences RNA processing, stability, localization, function, and degradation. Beyond its biological roles, RNA 3′-end modification has become a valuable tool in biotechnology, enabling applications in RNA labelling, sequencing, engineering and oligonucleotide synthesis. Terminal nucleotidyltransferases are key enzymes responsible for template-independent nucleotide addition to RNA molecules. Among these enzymes, Schizosaccharomyces pombe Cid1, a poly(U) polymerase, has emerged as an important model for understanding RNA-specific terminal nucleotidyltransferase activity. Structural and biochemical studies have revealed how nucleotide recognition, metal-ion-dependent catalysis, RNA positioning, and conformational dynamics regulate Cid1-mediated uridylation. Recent advances in protein engineering, molecular simulation, machine learning, and generative protein design have further expanded Cid1 functionality, generating variants with improved activity, altered substrate specificity, and potential applications in enzymatic RNA synthesis. This review summarizes the biological functions, structural characteristics, catalytic mechanisms, protein engineering strategies, and emerging biotechnological applications of Cid1, as well as the remaining challenges, highlighting its potential as a programmable platform for RNA 3′-end functionalization and enzymatic RNA oligonucleotide synthesis.
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BibTeX
@article{chen2026structurefunction,
title = {{Structure–Function Relationships of Cid1 Poly(U) Polymerase: Catalysis, Substrate Recognition, Engineering, and Applications}},
author = {Yang Chen and Pengbo Wang and Chenglong Zhang and Quanyong Liu and Kian Mau Goh and Shoutao Zhang},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101535},
url = {https://www.mdpi.com/2218-273X/16/10/1535},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Structure–Function Relationships of Cid1 Poly(U) Polymerase: Catalysis, Substrate Recognition, Engineering, and Applications
AU - Yang Chen
AU - Pengbo Wang
AU - Chenglong Zhang
AU - Quanyong Liu
AU - Kian Mau Goh
AU - Shoutao Zhang
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101535
UR - https://www.mdpi.com/2218-273X/16/10/1535
AB - RNA 3′-end modification is an important regulatory mechanism that influences RNA processing, stability, localization, function, and degradation. Beyond its biological roles, RNA 3′-end modification has become a valuable tool in biotechnology, enabling applications in RNA labelling, sequencing, engineering and oligonucleotide synthesis. Terminal nucleotidyltransferases are key enzymes responsible for template-independent nucleotide addition to RNA molecules. Among these enzymes, Schizosaccharomyces pombe Cid1, a poly(U) polymerase, has emerged as an important model for understanding RNA-specific terminal nucleotidyltransferase activity. Structural and biochemical studies have revealed how nucleotide recognition, metal-ion-dependent catalysis, RNA positioning, and conformational dynamics regulate Cid1-mediated uridylation. Recent advances in protein engineering, molecular simulation, machine learning, and generative protein design have further expanded Cid1 functionality, generating variants with improved activity, altered substrate specificity, and potential applications in enzymatic RNA synthesis. This review summarizes the biological functions, structural characteristics, catalytic mechanisms, protein engineering strategies, and emerging biotechnological applications of Cid1, as well as the remaining challenges, highlighting its potential as a programmable platform for RNA 3′-end functionalization and enzymatic RNA oligonucleotide synthesis.
SN - 2218-273X
ER -