Single-cell proteo-genomic reveals a comprehensive map of centrosome-associated spliceosome components
Luigi Cerulo,
Nunziana Pezzella,
Francesca Pia Caruso,
Paola Parente,
Andrea Remo,
Guido Giordano,
Nicola Forte,
Johan Busselez,
Federico Boschi,
Mirco Galiè,
Brunella Franco,
Massimo Pancione
Affiliations
Luigi Cerulo
Bioinformatics Laboratory, BIOGEM scrl, Ariano Irpino, Avellino, Italy; Department of Sciences and Technologies, University of Sannio, Benevento, Italy
Nunziana Pezzella
Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei, 34, Pozzuoli, 80078 Naples, Italy; School for Advanced Studies, Genomics and Experimental Medicine Program, Naples, Italy
Francesca Pia Caruso
Bioinformatics Laboratory, BIOGEM scrl, Ariano Irpino, Avellino, Italy; Department of Sciences and Technologies, University of Sannio, Benevento, Italy
Paola Parente
Unit of Pathology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
Andrea Remo
Pathology Unit, Mater Salutis Hospital AULSS9, “Scaligera”, 37122 Verona, Italy
Guido Giordano
Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, 71122 Foggia, Italy
Nicola Forte
Department of Clinical Pathology, Fatebenefratelli Hospital, 82100 Benevento, Italy
Johan Busselez
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
Federico Boschi
Department of Computer Science, University of Verona, Strada Le Grazie 8, Verona, Italy
Mirco Galiè
Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
Brunella Franco
Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei, 34, Pozzuoli, 80078 Naples, Italy; School for Advanced Studies, Genomics and Experimental Medicine Program, Naples, Italy; Medical Genetics, Department of Translational Medicine, University of Naples “Federico II”, Via Sergio Pansini, 80131 Naples, Italy; Corresponding author
Massimo Pancione
Department of Sciences and Technologies, University of Sannio, Benevento, Italy; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University Madrid, 28040 Madrid, Spain; Corresponding author
Summary: Ribonucleoprotein (RNP) condensates are crucial for controlling RNA metabolism and splicing events in animal cells. We used spatial proteomics and transcriptomic to elucidate RNP interaction networks at the centrosome, the main microtubule-organizing center in animal cells. We found a number of cell-type specific centrosome-associated spliceosome interactions localized in subcellular structures involved in nuclear division and ciliogenesis. A component of the nuclear spliceosome BUD31 was validated as an interactor of the centriolar satellite protein OFD1. Analysis of normal and disease cohorts identified the cholangiocarcinoma as target of centrosome-associated spliceosome alterations. Multiplexed single-cell fluorescent microscopy for the centriole linker CEP250 and spliceosome components including BCAS2, BUD31, SRSF2 and DHX35 recapitulated bioinformatic predictions on the centrosome-associated spliceosome components tissue-type specific composition. Collectively, centrosomes and cilia act as anchor for cell-type specific spliceosome components, and provide a helpful reference for explore cytoplasmic condensates functions in defining cell identity and in the origin of rare diseases.
