Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Improving Translational Accuracy02:07

Improving Translational Accuracy

8.6K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
8.6K
Initiation of Translation02:33

Initiation of Translation

30.4K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
30.4K
Leaky Scanning02:28

Leaky Scanning

5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

868
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
868
Regulated mRNA Transport02:22

Regulated mRNA Transport

6.2K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.2K
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

5.5K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
5.5K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

From classroom to clinic: the role of the clinical learning environment in shaping medical students' psychological capital.

BMC medical education·2026
Same author

The HY5-T5H1 Transcriptional Regulatory Module Enhances Chilling Stress by Promoting Serotonin Accumulation in Sea Buckthorn.

Journal of agricultural and food chemistry·2026
Same author

Genomic landscape and homologous recombination deficiency in malignant germ cell tumors reveals sex-specific therapeutic opportunities.

The Journal of pathology·2026
Same author

Vine-Inspired Twining Actuator: Cylindrical Hyper-Form-Closure Envelopment by Single Actuated Linkage.

Biomimetics (Basel, Switzerland)·2026
Same author

The authors reply.

Kidney international·2026
Same author

Roles of Wnt ligands and receptors in oral squamous cell carcinoma.

Journal of Zhejiang University. Science. B·2026
Same journal

TBX6 promotes proliferation, invasion, and migration in colorectal cancer: Integrated transcriptomic and protein interaction network analysis.

Gene·2026
Same journal

Face/off: phase-specific modeling of lineage plasticity using near-patient models in genitourinary cancers.

Gene·2026
Same journal

Hierarchical analysis of metabolic phenotype reveals distinct microbiota and circulatory transcriptome in metabolic dysfunction-associated steatotic liver disease.

Gene·2026
Same journal

Mutation T71R enhanced the structural stability and functional activity of wild type superoxide dismutase cloned from soil metagenome.

Gene·2026
Same journal

Reduced ATXN1 expression as an adverse prognostic indicator in Acute myeloid leukemia.

Gene·2026
Same journal

Constructing regulatory networks of Rubisco post-translational modifications: a novel avenue for engineering environment adaptive plants.

Gene·2026
See all related articles

Related Experiment Video

Updated: Jun 1, 2025

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
09:44

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes

Published on: March 3, 2015

9.4K

Optimizing mRNA translation efficiency through rational 5'UTR and 3'UTR combinatorial design.

Ting Li1, Gangfeng Liu2, Guolong Bu1

  • 1State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Gene
|January 17, 2025
PubMed
Summary
This summary is machine-generated.

Researchers optimized messenger RNA (mRNA) therapies by designing new untranslated regions (UTRs). Combining specific 5'UTR and 3'UTR sequences significantly boosted protein production for enhanced mRNA therapeutics.

Keywords:
3′UTR5′UTRTranslation efficiencyUTR combinationmRNA

More Related Videos

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
10:37

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

Published on: May 10, 2018

12.4K
Quantitative Immunofluorescence to Measure Global Localized Translation
09:13

Quantitative Immunofluorescence to Measure Global Localized Translation

Published on: August 22, 2017

9.8K

Related Experiment Videos

Last Updated: Jun 1, 2025

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
09:44

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes

Published on: March 3, 2015

9.4K
Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
10:37

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

Published on: May 10, 2018

12.4K
Quantitative Immunofluorescence to Measure Global Localized Translation
09:13

Quantitative Immunofluorescence to Measure Global Localized Translation

Published on: August 22, 2017

9.8K

Area of Science:

  • Molecular Medicine
  • Biotechnology
  • Genetic Engineering

Background:

  • Messenger RNA (mRNA)-based therapies show potential for treating diseases but face challenges like low translation efficiency and short half-life.
  • Untranslated regions (UTRs) critically regulate mRNA stability and translation efficiency, making them key targets for optimization.

Purpose of the Study:

  • To enhance exogenous mRNA translation efficiency through de novo design of 5'UTRs and combinatorial screening with 3'UTRs.
  • To identify novel UTR sequences and combinations that improve protein expression for mRNA therapeutics.

Main Methods:

  • A combinatorial screening strategy was employed to design and test novel 5'UTRs in combination with various 3'UTRs.
  • A novel 5'UTR, designated 5UTR05, was designed and its performance compared to a reference mRNA-1273 5'UTR.
  • Screening identified synergistic effects when combining 5UTR05 with specific 3'UTRs, including those from immunoglobulin heavy constant gamma 2 (IGHG2) and mitochondrially encoded 12S ribosomal RNA (mtRNR1).

Main Results:

  • The novel 5UTR05 demonstrated protein expression levels comparable to the high-performing mRNA-1273 5'UTR.
  • Combining 5UTR05 with both IGHG2 and mtRNR1 3'UTRs significantly enhanced mRNA translation efficiency compared to using individual 3'UTRs.
  • This synergistic combination resulted in superior protein expression, highlighting the importance of specific UTR pairings.

Conclusions:

  • Novel UTR designs and combinatorial strategies can effectively overcome limitations in exogenous mRNA translation efficiency.
  • The identified synergistic UTR combination (5UTR05 with IGHG2 and mtRNR1 3'UTRs) offers a promising approach for developing advanced mRNA therapeutics.
  • Further exploration of UTR combinations can lead to customized mRNA constructs with optimized expression for diverse therapeutic applications.