| Title: |
Evidence of distal regulations orchestrated by RNAs initiating at short tandem repeats |
| Authors: |
Grapotte, Mathys; Vroland, Christophe; Garrido-Martín, Diego; Vignoli, Alessio; Calero, Lisa; Bouvier, Quentin; Robin, Mathilde; Yip, Chi Wai; Carninci, Piero; Chatelain, Clement; Brehelin, Laurent; Notredame, Cedric; Guigó, Roderic; Lecellier, Charles-Henri |
| Contributors: |
Institut de Génétique Moléculaire de Montpellier (IGMM); Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); Centre for Genomic Regulation - Centre de Regulació Genòmica Barcelona (CRG); Universitat Pompeu Fabra Barcelona (UPF)-Centro Nacional de Analisis Genomico Barcelona (CNAG); Méthodes et Algorithmes pour la Bioinformatique (LIRMM; Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM); Université de Perpignan Via Domitia (UPVD)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université de Montpellier Paul-Valéry (UMPV)-Université de Perpignan Via Domitia (UPVD)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université de Montpellier Paul-Valéry (UMPV); Universitat de Barcelona (UB); Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM); CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); RIKEN Center for Integrative Medical Sciences Yokohama (RIKEN IMS); RIKEN - Institute of Physical and Chemical Research Japon (RIKEN); SANOFI Recherche; Barcelona Institute of Science and Technology (BIST); ANR-22-CE45-0031,LOWCO,Contribution des régions ADN de faible complexité dans les régulations génomiques(2022); ANR-22-PESN-0013,M4DI,Methods and models for multimodal and multi-scale data integration(2022) |
| Source: |
https://hal.science/hal-05030164 ; 2025. |
| Publisher Information: |
CCSD |
| Publication Year: |
2025 |
| Collection: |
Université de Perpignan: HAL |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
Short Tandem Repeats (STRs), also called microsatellites, correspond to tandemly repeated short DNA motifs (1 to 6 bp) and are one of the most polymorphic and abundant repetitive elements in the human genome. Variations of their length (i.e. number of consecutive repeats) have been implicated in gene expression regulation (termed expression(e)STRs). Using cap-trapping followed by long read sequencing, we discovered that STRs can host transcription start sites, the presence of which depends mainly on STR flanking sequences. Here, we investigate the effect of SNPs located in these sequences and ask whether STR-initiating RNAs have regulatory potential. First, we develop fully interpretable deep learning-based models, called Modular Neural Networks, able to predict, for each STR class, the level of RNAs using 101bp-long sequences encompassing STRs. Analysis of MNN filters allows us to identify multiple regulatory elements and candidate transcription factors. Second, leveraging genome sequencing and gene expression data from the Genotype-Tissue Expression project, we use the output of our models to link the levels of STR-initiating RNAs to the expression of nearby genes. We identify 14,340 significant associations (coined RNA(r)STRs) and illustrate how this novel resource can help interpret non-coding variants associated with complex traits and diseases. Third, we unveil an intricate transcriptional interplay between STR-initiating RNAs and Alu repeats that may couple their regulatory actions, extending both the nature and the functional importance of non-coding transcription and shedding new light on the complexity of distal regulations orchestrated by repeated sequences. |
| Document Type: |
report |
| Language: |
English |
| Relation: |
BIORXIV: 2025.04.10.648102 |
| DOI: |
10.1101/2025.04.10.648102 |
| Availability: |
https://hal.science/hal-05030164; https://hal.science/hal-05030164v1/document; https://hal.science/hal-05030164v1/file/2025.04.10.648102v1.full.pdf; https://doi.org/10.1101/2025.04.10.648102 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.52822387 |
| Database: |
BASE |