Evidence map›Paper›PMID 40823812›Full record

ArticleNucleic acids research2025

Internal ribosome entry sites enhance translation in trans in antisense non-coding SINEUP and circular RNAs.

Sabrina D'Agostino, Abraham Tettey-Matey, Massimiliano Volpe, Bianca Pierattini, Mattia D'Agostino, Denisa Smělá, Federico Ansaloni, Laura Broglia, Pierre Lau, Omar Peruzzo and 19 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Sabrina D'AgostinoCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.ORCID 0000-0002-4858-8873
Abraham Tettey-MateyArea of Neuroscience, International School for Advanced Studies (SISSA), Trieste, Italy.
Massimiliano VolpeCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Bianca PierattiniCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.ORCID 0000-0001-5023-7629
Mattia D'AgostinoArchitecture et Réactivité de l'ARN, CNRS UPR 9002, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg, France.
Denisa SměláCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Federico AnsaloniCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Laura BrogliaCenter for Human Technologies, RNA Systems Biology, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.ORCID 0000-0003-2099-7373
Pierre LauCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Omar PeruzzoCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Clarissa BracciaD3 Pharmachemistry, Istituto Italiano di Tecnologia (IIT), Via Morego, 30, Genova 16163, Italy.
Andrea ArmirottiAnalytical Chemistry Lab, Istituto Italiano di Tecnologia (IIT), Via Morego, 30, Genova 16163, Italy.ORCID 0000-0002-3766-8755
Margherita ScarpatoCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Devid DamianiCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Gloria RosCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Valerio Di CarloCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Federica ManiscalcoCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Elias BecharaCenter for Human Technologies, RNA Systems Biology, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.
Gian Gaetano TartagliaCenter for Human Technologies, RNA Systems Biology, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.ORCID 0000-0001-7524-6310
Piero CarninciRIKEN Center for Integrative Medical Sciences (IMS), Yokohama 230-0045, Japan.ORCID 0000-0001-7202-7243
Claudio SantoroDepartment of Health Sciences and Research Center on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale (UPO), Novara, Italy.ORCID 0000-0002-4552-9624
Francesca PersichettiDepartment of Health Sciences and Research Center on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale (UPO), Novara, Italy.ORCID 0000-0002-9804-644X
Luca PandolfiniCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.ORCID 0000-0003-1444-8167
Angelita SimonettiArchitecture et Réactivité de l'ARN, CNRS UPR 9002, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg, France.
Stefano EspinozaCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.ORCID 0000-0002-3048-4822
Silvia ZucchelliDepartment of Health Sciences and Research Center on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale (UPO), Novara, Italy.
Remo SangesCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.ORCID 0000-0002-5047-9713
Carlotta BonCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.ORCID 0000-0002-7443-4659
Stefano GustincichCenter for Human Technologies, Non-coding RNAs and RNA-based therapeutics, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen 83, Genova 16152, Italy.ORCID 0000-0002-2749-2514

Funding

Ministero dell'Università della Ricerca (MIUR) Bando PRIN 2017-Prot. 2017SNRXH3National Center for Gene Therapy and Drug based on RNA Technology CN00000041NextGenerationEUPotenziamento strutture di ricerca e di campioni nazionali di R&S CUP J33C22001130001
6 · The paper itself

Abstract

Sequences in the 5'-untranslated regions of cellular and viral mRNAs can function as internal ribosome entry sites (IRESs), driving cis-acting translation of the downstream protein-coding open reading frame. Here we demonstrate that RNA sequences with either newly identified or well-characterized IRES activity can also induce trans-acting translation of an independent mRNA species through an antisense sequence. SINEUPs are antisense long non-coding RNAs that enhance the translation of overlapping sense mRNAs in trans by employing two critical domains: the invSINEB2 sequence, which up-regulates translation (effector domain), and an antisense region providing target specificity (binding domain). First, we show that the invSINEB2 from the natural SINEUP AS Uchl1 RNA acts as an IRES when functioning in cis. Next, we establish that known viral and cellular sequences with IRES activity can operate in trans as an effector domain in synthetic SINEUPs. To identify natural IRES-containing non-coding RNAs with transactivity, we found that the non-coding hsa_circ_0 085 533 (circMyc), transcribed from the c-myc locus, enhances protein expression of PX Domain Containing Serine/Threonine Kinase Like (PXK) by promoting mRNA association with polysomes through antisense sequences. These results suggest that SINEUPs and some circular RNAs are trans-acting IRESs, expanding the repertoire of molecular mechanisms to regulate translation.

Indexed as

Internal Ribosome Entry SitesProtein BiosynthesisRNA, AntisenseRNA, CircularRNA, Long Noncoding5' Untranslated RegionsHumansOpen Reading FramesRibosomesRNA, Messenger5' Untranslated RegionsInternal Ribosome Entry SitesRNA, AntisenseRNA, CircularRNA, Long NoncodingRNA, Messenger

Identifiers

PMID40823812
PMCPMC12359042

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