Evolutionary emergence and preservation of microproteins encoded by upstream ORFs
The analysis of ribosome profiling (Ribo-Seq) data has provided evidence that many eukaryotic mRNAs contain translated upstream or downstream ORFs (uORFs/dORFs), but the biological significance of this translation activity remains, for the most part, unknown. One of the principal limitations has been the lack of Ribo-Seq data from several closely related species, precluding the identification of cases in which translation is phylogenetically conserved. Here, by combining Ribo-Seq data from 100 different experiments, we identify 2,332 translated uORFs and 1,008 translated dORFs in S. cerevisiae, which result in microproteins that tend to be highly hydrophobic or positively charged. To study their phylogenetic conservation, we have generated Nanopore direct RNA sequencing data, together with Ribo-Seq data, from six additional Saccharomyces species, spanning an evolutionary period of around 16 million years. We have identified 195 translated S. cerevisiae uORFs that are also translated in other Saccharomyces species; these uORFs are translated at levels comparable to the main coding sequence and display signatures of purifying selection at the level of the encoded microproteins. In contrast, dORFs are translated at very low levels and they are rarely conserved, suggesting much more limited microprotein functionalization. We have also discovered that uORF translation is associated with the formation of alternative transcript isoforms encompassing the region containing the uORFs but not the main protein coding sequence, implying that some microproteins can be produced independently of the main protein product. This work significantly advances our understanding of how initially pervasive uORF translation can result in new microproteins, providing many new candidates for further functional studies. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90, 101052538 Ministerio de Ciencia, Innovaciรณn y Universidades, PID2021- 122726NBI00, PGC2018-094091- B-I00, PID2022-136939OBI00, CEX2024-001431-M, MICIU/AEI/10.13039/501100011033 Generalitat de Catalunya, https://ror.org/01bg62x04, 2021SGR00042, 2021SGR00176
New preprint from the group!
Here we use Nanopore dRNA and Ribo-Seq data from multiple yeast species to discover tens of highly conserved microproteins encoded by uORFs in polycistronic transcripts/alternative isoforms. @prbb.org @grib-barcelona.bsky.social
www.biorxiv.org/content/10.6...
08.03.2026 19:13
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The work, published in @thelancet.com, analyzes comorbidities, medication use, and overall survival in more than 1.7 million people diagnosed with eight types of cancer in Europe
@ibis-investigacion.bsky.social
18.02.2026 09:21
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An international study coordinated by the IDIAPJGol, with participation from @hospitaldelmar.bsky.social and Hospital del Mar Research Institute, has produced the most detailed picture to date of the cancer situation in Europe
#oncology
www.researchmar.net/news/803/a-l...
18.02.2026 09:21
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The Hospital del Mar Research Institute has appointed Judit Cubedo as the new Managing Director
The appointment of Judit Cubedo represents a strategic reinforcement at a key moment for institutional consolidation
#TalentMAR @hospitaldelmar.bsky.social
researchmar.net/news/804/jud...
19.02.2026 10:11
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Today we celebrate the International Day of Women and Girls in Science! ๐๐ฌ At GRIB, we honor the brilliant women๐ driving innovation and discovery in computational biology and beyond. Letโs keep pushing for #equity, #representation, and #excellence in science.
@prbb.org @researchmar.bsky.social
11.02.2026 11:23
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Distinct DNA-binding syntax and chromatin remodeling capacities of bHLH transcription factors in cell differentiation, reprogramming and cancer https://www.biorxiv.org/content/10.64898/2026.02.10.705010v1
11.02.2026 10:18
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Weโre excited to share our new preprint on the mechanisms underlying DNA binding by bHLH transcription factors and how they achieve distinct DNA binding specificities. The study has been spearheaded by Xabier de Martรญn.
@grib-barcelona.bsky.social
Take a look! ๐
www.biorxiv.org/content/10.6...
11.02.2026 09:30
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Treatment-resistant #depression identified as a distinct molecular subtype
An international study in @brainbehavimm.bsky.social shows that these patients have a unique biology
#research #mentalhealth @jupererabel.bsky.social @grib-barcelona.bsky.social
www.researchmar.net/news/763/tre...
31.10.2025 09:16
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S'han identificat mรฉs de 5.000 gens que es comporten de manera diferent en aquesta patologia, en comparaciรณ amb els pacients no resistents
@grib-barcelona.bsky.social @jupererabel.bsky.social @uni-muenster.de @upf.edu
31.10.2025 11:10
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๐ซ Another year, another #OpenPRBB!! ๐ซ
๐ฌ ๐ฉโ๐ฌ ๐จโ๐ป
Last Saturday, October 4, @prbb.org opened its doors to the public to discover what #science is doing from within ๐๐
Some of the members of the GRIB Barcelona have participated ๐ฅณ
08.10.2025 08:49
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En bones mans 20/07/2025
Programa complet 'En bones mans', amb Robert Calvo. Fem salut des de la rร dio.
La Dra. Jana Selent respon les preguntes d'en @robertcalvo.bsky.social ๐๏ธ sobre el paper dels #aminoร cids a la resposta de les cรจlยทlules davant els #fร rmacs
Al programa En bones mans d'@ondacero.es ๐ป
#bioinformร tica @grib-barcelona.bsky.social
www.ondacero.es/emisoras/cat...
23.07.2025 13:45
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This is the conclusion of an international study led by the Hospital del Mar Research Institute, published in Nature Communications
The findings may help develop more precise drugs to treat various diseases more effectively, while avoiding side effects
@upf.edu @hospitaldelmar.bsky.social
16.07.2025 07:15
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Amino acids play a key role in how cells respond to drugs
These molecules act as small building blocks that regulate the cellular response by switching certain internal signals on or off
#aminoacids #drugs #biomedicalinformatics @grib-barcelona.bsky.social
www.researchmar.net/news/731/ami...
16.07.2025 07:15
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Early developmental origins of cortical disorders modeled in human neural stem cells
Nature Communications - The implications of early telencephalic development in cortical disorders remain elusive. Here, the authors define risk gene dynamics and perturbation effects in neural stem...
Excited to share our latest work, spearheaded by my brilliant student Xoel Mato and co-led by Nicola Micali. After years of sweat, intense weekly meetings, and meticulous discussion of every panel, we learned a lot from each other. Grateful for the journey!
@researchmar.bsky.social
rdcu.be/evCaU
10.07.2025 06:24
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Great PhD defence today of Lili Boll on combining large amounts of omics data to better understand Immune Checkpoint Inhibitor response!
@upf.edu @grib-barcelona.bsky.social
08.07.2025 19:37
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๐We have reached the end of the #PRBBComputationalGenomics course!! These seminars brings together the computational genomics community of
@prbb.org, promoting work between institutions and strengthening links between different #research groups๐ฅ๐ฉโ๐ป
07.07.2025 09:28
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Join our Cloud HD Video Meeting
Zoom is the leader in modern enterprise cloud communications.
๐ฉโ๐ป On 8th July, Lilian Boll, member of the Evolutionary Genomics Group, will defend her #Thesis "Decoding Immune Checkpoint Inhibitor Response - Biomarker Discovery and Predictive Modeling through Multi-omics analyses" ๐
โฐ 10h- ๐ 61.210 room of campus Mar - ๐ฅ๏ธ upf-edu.zoom.us/j/96662263541
07.07.2025 09:26
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Diversity is in our #DNA๐งฌ
At @grib-barcelona.bsky.social, science thrives through #inclusion and #pride๐ณ๏ธโ๐
#PrideMonth #ScienceWithPride
@researchmar.bsky.social @prbb.org
04.06.2025 08:03
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Lili gave a talk entitled "Refining Immunotherapy Response Prediction in Advanced Bladder Cancer" related to the work recently published by the group in Nature Communications Check it out๐ ๐
pubmed.ncbi.nlm.nih.gov/39979258/
26.05.2025 07:44
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Lilian Marie Boll and Marta Espinosa Camarena presented their work at the congress of the European Association for Cancer Research (EACR) "Defence is the Best Attack: Immuno-Oncology Breakthroughs" celebrated at the CosmoCaixa 13 - 15 May 2025.
@prbb.org @researchmar.bsky.social
26.05.2025 07:43
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Last week we attended the #ECCN2025 meeting in Alacant. It was an impressive succession of mind-blowing talksโexhilarating and exhausting. You couldnโt let your guard down for a second!
Here are Paula Mayo and Josema Ruiz presenting their posters.
@grib-barcelona.bsky.social
14.05.2025 08:04
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๐Last week (28-29 April), members of @grib-barcelona.bsky.social attended the Computational Genomics Symposium 2025 in Sant Feliu de Guixols, Girona!โ๏ธ๐โโ๏ธ
@maralbalab.bsky.social @researchmar.bsky.social @prbb.org
08.05.2025 09:47
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๐ฒ We wish you a very good day of #SantJordi2025!๐นโ๏ธ
@prbb.org @researchmar.bsky.social @upf.edu
23.04.2025 09:08
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๐ฐ GRIB NEWS!๐ฐ
๐New pathways discovered for #drugs to act on #cells
Unknow access points in cell membrane #proteins, enabling laboratory-developed drugs to modify cell function๐
Published by @naturecomms.bsky.social
๐ grib.upf.edu/new-pathways...
27.03.2025 09:06
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Big data to predict response to immunotherapy - Elยทlipse
The study from Hospital del Mar Research Institute and MELIS-UPF within the programme GRIB has focused on bladder cancer.
๐ฌ@maralbalab.bsky.socialย @jupererabel.bsky.socialย @oncobellmunt.bsky.socialย @robertclab.bsky.socialย team have developed a machine learning algorithm to see how bladder cancer patients respond to immunotherapy.
@grib-barcelona.bsky.socialย @researchmar.bsky.socialย @upf.edu
More๐
21.03.2025 16:13
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๐ Today and always, we stand for equality! ๐
On Saturday, the #8M reminded us of the #fight, the #strength, and the journey still ahead. Letโs keep raising our voices for a fairer world for all. โโจ
#InternationalWomensDay #8M #Equality
10.03.2025 09:11
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