Research Field

Computational Biology

AI models uncover the regulatory grammar of nucleic acids across genomes, cells, and populations.

C - Nucleic Acid Metabolism & Homeostasis
C1

Description

Advances in sequencing technologies now capture diverse layers of nucleic acid biology, from genome sequence and epigenetic regulation to gene expression, RNA processing, and protein–RNA interactions. This research area seeks to integrate these molecular modalities to uncover the principles that govern gene regulation, genetic variation, and disease.

A central goal is to develop advanced AI models capable of learning meaningful representations of nucleic acid sequences and their regulatory contexts across multiple biological scales. The research combines large-scale genomic, transcriptomic, epigenomic, and single-cell datasets to identify regulatory mechanisms, interpret disease-associated genetic variation, and link molecular phenotypes to cellular function. Particular emphasis is placed on integrating multimodal data and developing foundation models that capture the underlying grammar of nucleic acid regulation. By transforming complex biological datasets into predictive frameworks, the project aims to reveal previously inaccessible regulatory principles and accelerate the discovery of disease mechanisms and therapeutic targets.

Area C1

Researchers

C1
Associated Investigator

Prof. Dr.

Maria Colomé-Tatché

Biomedical Center and Department Physiological Chemistry, Faculty of Medicine

Ludwig-Maximilians-Universität München

C1
Principal Investigator

Prof. Dr.

Sarah Kim-Hellmuth

Independent Research Group Leader, Department of Pediatrics and Institute of Translational Genomics

Klinikum der Ludwig-Maximilians-Universität München and Helmholtz Zentrum München

C1
Associated Investigator

Prof. Dr.

Annalisa Marsico

Research group leader, Institute of Computational Biology, Computational Health Center

Helmholtz Zentrum München

C1
Associated Investigator

Prof. Dr.

Emmanuel Saliba

Professor Single Cell Analysis, Institute of Molecular Infection Biology, Faculty of Medicine and Group Leader, Helmholtz Institute of RNA-based Infection Research (HIRI)

Julius-Maximilians-Universität Würzburg and Helmholtz Institut für RNA-basierte Infektionsforschung (HIRI)

C1
Principal Investigator

Prof. Dr.

Fabian Theis

Chair of Mathematical Modelling of Biological Systems, Director, Institute of Computational Biology and Department of Mathematics, TUM School of Computation, Information and Technology

Helmholtz Zentrum München and Technische Universität München

A2
C1
B2
Associated Investigator

Prof. Dr.

Kathi Zarnack

Chair of Bioinformatics II, Theodor Boveri Institute, Biocenter, Faculty of Biology

Julius-Maximilians-Universität Würzburg

C1
C3
Associated Investigator

Prof. Dr.

Eleftheria Zeggini

Professor of Translational Genomics, Institute of Translational Genomics, Computational Health Center

Helmholtz Zentrum München

Area C1

Publications

SAM68 is a multifunctional post-transcriptional regulator of cardiomyocyte differentiation.

Broglia, L.; Dasti, A.; Antonelli, MC.; Aoun, G.; D'Agostino, S.; Vandelli, A.; Armaos, A.; Delli Ponti, R.; Wolf, S.; Klostermann, M.; Arnal Segura, M.; Tian, TV.; Mariani, D.; Colantoni, A.; Paronetto, MP.; Gustincich, S.; Zarnack, K.; Bechara, E.; Tartaglia, GG.

Nucleic Acids Res. · 2026

Show abstract

RNA-binding proteins (RBPs) of the STAR family play key roles in mammalian development, yet their contributions to lineage specification remain incompletely understood. Here, using CRISPR-Cas9 knockout models combined with multi-omics approaches, we investigate the functions of two STAR proteins, SAM68 and QKI, in mouse embryonic stem cells (mESCs). Both RBPs support mESC proliferation, self-renewal, and efficient differentiation into cardiomyocytes. Although SAM68 and QKI belong to the same protein family, they control largely distinct regulatory programs during differentiation. We uncover an unexpected role for SAM68 in cardiomyocyte specification through multiple post-transcriptional mechanisms. SAM68 modulates alternative splicing and promotes the biogenesis of a subset of cardiac-enriched circular RNAs, through binding to intronic regions flanking back-splice junctions and potentially through association with NF90/110. In addition, SAM68 binds untranslated regions of key differentiation-related transcripts, including Gata4 mRNA, and functions in ribonucleoprotein complexes to regulate their translation. Together, these findings identify SAM68 as a multifunctional regulator coordinating multiple layers of RNA metabolism-including splicing, circRNA biogenesis, and translation-during cardiomyocyte differentiation and provide insight into how STAR proteins shape post-transcriptional gene regulatory networks during early development.

RNA motifs, RNA structure, and motif context analyzed by RNAanalyzer3.

Akash, A.; Balkenhol, J.; Liang, C.; Zarnack, K.; Dandekar, T.

Nucleic Acids Res. · 2026

Show abstract

RNAanalyzer3 ("RNA analyzer cubic"; https://rnaanalyzer.bioapps.biozentrum.uni-wuerzburg.de) substitutes the frequently consulted current RNAanalyzer webserver (https://rnaanalyzer-old.bioapps.biozentrum.uni-wuerzburg.de). RNAanalyzer3 is free/open via the secure HTTPS protocol, with example data, help and tutorial, web-link to results, and rich data output. We combine a general detailed structure analysis with motif analyses. It accepts either a single plain-text nucleotide sequence or batch submission in FASTA format, which can be pasted or uploaded as a FASTA file. Our tool (i) has up-to-date software and operating systems, (ii) combines diverse RNA motif analyses with RNA structure prediction, (iii) puts found motifs into structural context, and (iv) offers dedicated tools for probing RNA-protein binding interactions. RNAanalyzer3 links motif searches to Rfam and miRNA search to miRbase. It focuses on structural features first, looks for stem-loops, hairpins, and specific enrichment regions such as stem-GG pairs, plus AU-rich regions with their locations for easier identification, while providing structural context and interactive RNA structure visualization. A tabulated overview shows all RNA features including structure details, coding potential, untranslated regions (UTRs, including Shine-Dalgarno sequences, Kozak sequences, and polyadenylation signals), transfer RNA (tRNA), microRNA (miRNA), long noncoding RNA (lncRNA), trans-splicing motifs, iron response elements (IRE), riboswitches, small nuclear ribonucleoprotein (snRNP) motifs, and spliceosomal Sm-sites.