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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...

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Related Experiment Video

Updated: May 14, 2026

An Integrated Approach for Microprotein Identification and Sequence Analysis

An Integrated Approach for Microprotein Identification and Sequence Analysis

Published on: July 12, 2022

miR-1289 and "Zipcode"-like Sequence Enrich mRNAs in Microvesicles.

Mehmet Fatih Bolukbasi¹, Arda Mizrak, Gokhan Baris Ozdener

¹Department of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Molecular Therapy. Nucleic Acids

|January 25, 2013

Summary

Researchers discovered a specific RNA sequence that acts like a postal code, directing messenger RNA (mRNA) into microvesicles (MVs). This finding sheds light on how genetic material is packaged and released by cells.

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Area of Science:

Molecular Biology
Cell Biology
Genetics

Background:

The mechanisms for packaging genetic material into microvesicles (MVs) remain largely unknown.
Microvesicles play crucial roles in intercellular communication and disease progression.

Purpose of the Study:

To identify the molecular mechanisms responsible for the enrichment of specific messenger RNAs (mRNAs) within microvesicles.
To characterize a novel sequence element involved in mRNA targeting to MVs.

Main Methods:

Bioinformatic analysis of mRNA sequences enriched in MVs compared to glioblastoma cells.
In vitro reporter assays to test the function of the identified sequence.
Quantitative analysis of mRNA and microRNA levels.

Main Results:

A 25-nucleotide (nt) sequence in the 3'-untranslated region (3'UTR) of mRNAs was identified as a potential targeting signal for MVs.
Variants of this sequence were found in mRNAs highly enriched in MVs.
Incorporating this sequence into a reporter mRNA led to its enrichment in MVs.
The sequence features a CUGCC core within a stem-loop structure and a microRNA (miRNA) binding site.
Increased levels of the corresponding miRNA enhanced mRNA enrichment in MVs.

Conclusions:

A novel zipcode-like sequence in the 3'UTR of mRNAs mediates their selective packaging into microvesicles.
This sequence, containing a specific RNA structure and miRNA binding site, is a key determinant of mRNA MV enrichment.
Understanding this mechanism offers insights into MV biogenesis and potential therapeutic strategies.