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Evaluating Malat1-derived 3'end sequences for functional transgene expression in human cells using synthetic mRNA
Julia Rosemann1,2, Gwendolin Thordis Jahr1, Jana Macho1
1Institute of Molecular Medicine, Section for RNA Biology and Pathogenesis, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
RNA Biology
|May 7, 2026
Summary
Researchers explored using Malat1 RNA structures as alternatives to poly(A) tails for messenger RNA. While Malat1 motifs supported translation, they were less effective than traditional poly(A) tails.
Area of Science:
- Molecular Biology
- RNA Biology
- Biochemistry
Background:
- The poly(A) tail is crucial for messenger RNA (mRNA) stability and translation in mammals.
- The long non-coding RNA Malat1 has a unique 3' end structure involving a triple helix.
- This Malat1 triple helix has shown potential to enhance translation.
Purpose of the Study:
- To evaluate Malat1-derived sequence elements as potential replacements for canonical poly(A) tails.
- To compare the translational efficiency of Malat1 motifs versus poly(A) tails in a synthetic reporter system.
Main Methods:
- Constructed synthetic reporter RNAs encoding green fluorescent protein.
- Incorporated Malat1-derived 3' end motifs and canonical poly(A) tails into reporter RNAs.
- Quantified and compared the expression levels driven by each 3' end element.
Main Results:
- Malat1-derived motifs supported reporter mRNA translation.
- Canonical poly(A) tails consistently outperformed Malat1 motifs in driving reporter gene expression.
- The study confirmed the essential role of poly(A) tails for efficient mRNA expression.
Conclusions:
- Malat1-derived triple helix structures can support mRNA translation but are less efficient than poly(A) tails.
- Further optimization of Malat1 triplex structures is needed to improve translational capacity.
- These findings have implications for synthetic biology and RNA-based therapeutics.
