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Regulation of Expression at Multiple Steps

Regulation of Expression at Multiple Steps

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...

Regulated mRNA Transport

Regulated mRNA Transport

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...

Regulation of Expression Occurs at Multiple Steps

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...

Alternative RNA Splicing

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...

Chromatin Structure Regulates pre-mRNA Processing

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...

Types of RNA

Types of RNA

Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...

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Related Experiment Video

Updated: Jun 2, 2025

An Efficient Strategy for Generating Tissue-specific Binary Transcription Systems in Drosophila by Genome Editing

An Efficient Strategy for Generating Tissue-specific Binary Transcription Systems in Drosophila by Genome Editing

Published on: September 19, 2018

A generative framework for enhanced cell-type specificity in rationally designed mRNAs.

Matvei Khoroshkin^1,2,3,4, Arsenii Zinkevich⁵, Elizaveta Aristova⁵

¹Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.

Biorxiv : the Preprint Server for Biology

|January 13, 2025

Summary

This summary is machine-generated.

Researchers developed PARADE, an AI framework for designing highly stable messenger RNA (mRNA) with precise cell type specificity. This platform enhances mRNA therapies, improving stability, efficacy, and reducing tumor growth in preclinical models.

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An Efficient Strategy for Generating Tissue-specific Binary Transcription Systems in Drosophila by Genome Editing

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Published on: September 19, 2018

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Isolate Cell-Type-Specific RNAs from Snap-Frozen Heterogeneous Tissue Samples without Cell Sorting

Isolate Cell-Type-Specific RNAs from Snap-Frozen Heterogeneous Tissue Samples without Cell Sorting

Published on: December 8, 2021

Area of Science:

Molecular Biology
Bioengineering
Artificial Intelligence

Background:

Messenger RNA (mRNA) therapeutics offer promise for disease treatment by enabling cellular production of therapeutic proteins.
Current challenges include engineering mRNA with high stability and programmable cell type-specific delivery.
Untranslated regions (UTRs) of mRNA play a critical role in regulating gene expression and stability.

Purpose of the Study:

To develop a computational framework for designing mRNA untranslated regions (UTRs) with enhanced stability and cell type-specific activity.
To engineer novel mRNA sequences for improved therapeutic applications.
To validate the efficacy of designed mRNA UTRs in preclinical models.

Main Methods:

Measured regulatory activity of 60,000 5' and 3' UTRs across six cell types.
Developed PARADE (Prediction And RAtional DEsign of mRNA UTRs), a generative AI framework.
Validated 15,800 de novo-designed sequences in cell lines and animal models.
Tested PARADE-engineered UTRs in oncosuppressor mRNAs (PTEN, P16) in tumor models.

Main Results:

PARADE identified novel UTR sequences with superior cell type specificity and activity compared to existing RNA therapeutics.
Engineered mRNAs demonstrated robust tissue-specific expression in vivo (liver, spleen).
PARADE enhanced mRNA stability, leading to increased protein output and therapeutic durability.
PARADE-designed UTRs significantly reduced tumor growth in neuroglioma xenograft and orthotopic mouse models.

Conclusions:

PARADE is a versatile AI platform for designing precise, stable, and effective mRNA therapies.
The framework enables rational engineering of mRNA UTRs for targeted therapeutic applications.
This approach holds potential for advancing the development of next-generation mRNA-based medicines.