RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H matrix screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks. The dataset we provide will be a valuable resource for understanding the combinatorial interactions of RBPs with RNAs and the resulting regulatory outcomes.

Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins / Lang, Benjamin; Yang, Jae-Seong; Garriga-Canut, Mireia; Speroni, Silvia; Aschern, Moritz; Gili, Maria; Hoffmann, Tobias; Tartaglia, GIAN GAETANO; Maurer, Sebastian~p. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 49:12(2021), pp. 6702-6721. [10.1093/nar/gkab490]

Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins

Gian Gaetano Tartaglia;
2021

Abstract

RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H matrix screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks. The dataset we provide will be a valuable resource for understanding the combinatorial interactions of RBPs with RNAs and the resulting regulatory outcomes.
2021
RBPs; rec-Y2H matrix; gene regulation; mammalian RBPs
01 Pubblicazione su rivista::01a Articolo in rivista
Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins / Lang, Benjamin; Yang, Jae-Seong; Garriga-Canut, Mireia; Speroni, Silvia; Aschern, Moritz; Gili, Maria; Hoffmann, Tobias; Tartaglia, GIAN GAETANO; Maurer, Sebastian~p. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 49:12(2021), pp. 6702-6721. [10.1093/nar/gkab490]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1626504
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