A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in <i>E. coli</i>

Circular RNA (circRNA) exhibits a higher stability and intracellular half-life than linear RNA and has better potential in the fields of RNA vaccines and RNAi drugs. The current strategies for circRNA preparation have low efficiency, high costs, and high complexity, which significantly limits their...

Full description

Saved in:
Bibliographic Details
Main Authors: Xiayang Zhao, Yiqing Liu, Huanhui Huang, Yue Sun, Fangli Wu, Weibo Jin
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/14/11/1416
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850267763530006528
author Xiayang Zhao
Yiqing Liu
Huanhui Huang
Yue Sun
Fangli Wu
Weibo Jin
author_facet Xiayang Zhao
Yiqing Liu
Huanhui Huang
Yue Sun
Fangli Wu
Weibo Jin
author_sort Xiayang Zhao
collection DOAJ
description Circular RNA (circRNA) exhibits a higher stability and intracellular half-life than linear RNA and has better potential in the fields of RNA vaccines and RNAi drugs. The current strategies for circRNA preparation have low efficiency, high costs, and high complexity, which significantly limits their applications. In this paper, we propose a one-step synthesis of circRNA based on <i>E. coli.</i> The four RNA sequence lengths of 1700, 1400, 500, and 64 nt were connected to group II intron elements from the surface protein region of <i>Clostridium tetani</i> and then inserted downstream of the T7 promoter in the pET28a plasmid to assist in cyclization. Then, circRNA was produced in HT115, where the yields of pET28-1700, pET28-1400, pET28-500, and pET28-64 were improved to 820, 783, 691, and 460 ng/1 mL, respectively. Consequently, this system could achieve the mass production of circRNA using only a simple <i>E. coli</i> culture and inducible expression. Meanwhile, the overexpressed circRNA and small circular interference RNA (sciRNA) maintained their biological functions in the protein translation and RNAi. Therefore, this simple and efficient one-step synthesis system can be applied to the functional study and preparation of circRNA in the future.
format Article
id doaj-art-e911e12f6ef8476c8e294512ca10816d
institution OA Journals
issn 2218-273X
language English
publishDate 2024-11-01
publisher MDPI AG
record_format Article
series Biomolecules
spelling doaj-art-e911e12f6ef8476c8e294512ca10816d2025-08-20T01:53:40ZengMDPI AGBiomolecules2218-273X2024-11-011411141610.3390/biom14111416A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in <i>E. coli</i>Xiayang Zhao0Yiqing Liu1Huanhui Huang2Yue Sun3Fangli Wu4Weibo Jin5Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaKey Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaKey Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaZhejiang Sci-Tech University Shaoxing Academy of Biomedicine, Zhejiang Sci-Tech University, Shaoxing 312366, ChinaKey Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaKey Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCircular RNA (circRNA) exhibits a higher stability and intracellular half-life than linear RNA and has better potential in the fields of RNA vaccines and RNAi drugs. The current strategies for circRNA preparation have low efficiency, high costs, and high complexity, which significantly limits their applications. In this paper, we propose a one-step synthesis of circRNA based on <i>E. coli.</i> The four RNA sequence lengths of 1700, 1400, 500, and 64 nt were connected to group II intron elements from the surface protein region of <i>Clostridium tetani</i> and then inserted downstream of the T7 promoter in the pET28a plasmid to assist in cyclization. Then, circRNA was produced in HT115, where the yields of pET28-1700, pET28-1400, pET28-500, and pET28-64 were improved to 820, 783, 691, and 460 ng/1 mL, respectively. Consequently, this system could achieve the mass production of circRNA using only a simple <i>E. coli</i> culture and inducible expression. Meanwhile, the overexpressed circRNA and small circular interference RNA (sciRNA) maintained their biological functions in the protein translation and RNAi. Therefore, this simple and efficient one-step synthesis system can be applied to the functional study and preparation of circRNA in the future.https://www.mdpi.com/2218-273X/14/11/1416group II introncircularization in vivoone-step synthesissciRNAcondition optimization
spellingShingle Xiayang Zhao
Yiqing Liu
Huanhui Huang
Yue Sun
Fangli Wu
Weibo Jin
A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in <i>E. coli</i>
Biomolecules
group II intron
circularization in vivo
one-step synthesis
sciRNA
condition optimization
title A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in <i>E. coli</i>
title_full A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in <i>E. coli</i>
title_fullStr A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in <i>E. coli</i>
title_full_unstemmed A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in <i>E. coli</i>
title_short A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in <i>E. coli</i>
title_sort simple and efficient one step synthesis system for flexible production of circular rna in i e coli i
topic group II intron
circularization in vivo
one-step synthesis
sciRNA
condition optimization
url https://www.mdpi.com/2218-273X/14/11/1416
work_keys_str_mv AT xiayangzhao asimpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT yiqingliu asimpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT huanhuihuang asimpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT yuesun asimpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT fangliwu asimpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT weibojin asimpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT xiayangzhao simpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT yiqingliu simpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT huanhuihuang simpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT yuesun simpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT fangliwu simpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii
AT weibojin simpleandefficientonestepsynthesissystemforflexibleproductionofcircularrnainiecolii