caa a22 4500 463209397 CHVBK 20180405153135.0 cr unu---uuuuu 170326e20070201xx s 000 0 eng 10.1007/s00412-006-0083-3 doi (NATIONALLICENCE)springer-10.1007/s00412-006-0083-3 FRG1P-mediated aggregation of proteins involved in pre-mRNA processing [Elektronische Daten] [Silvana van Koningsbruggen, Kirsten Straasheijm, Ellen Sterrenburg, Natascha de Graaf, Hans Dauwerse, Rune Frants, Silvère van der Maarel] FRG1 is considered a candidate gene for facioscapulohumeral muscular dystrophy (FSHD) based on its location at chromosome 4qter and its upregulation in FSHD muscle. The FRG1 protein (FRG1P) localizes to nucleoli, Cajal bodies (and speckles), and has been suggested to be a component of the human spliceosome but its exact function is unknown. Recently, transgenic mice overexpressing high levels of FRG1P in skeletal muscle were described to present with muscular dystrophy. Moreover, upregulation of FRG1P was demonstrated to correlate with missplicing of specific pre-mRNAs. In this study, we have combined colocalization studies with yeast two-hybrid screens to identify proteins that associate with FRG1P. We demonstrate that artificially induced nucleolar aggregates of VSV-FRG1P specifically sequester proteins involved in pre-mRNA processing. In addition, we have identified SMN, PABPN1, and FAM71B, a novel speckle and Cajal body protein, as binding partners of FRG1P. All these proteins are, or seem to be, involved in RNA biogenesis. Our data confirm the presence of FRG1P in protein complexes containing human spliceosomes and support a potential role of FRG1P in either splicing or another step in nuclear RNA biogenesis. Intriguingly, among FRG1P-associated proteins are SMN and PABPN1, both being involved in neuromuscular disorders, possibly through RNA biogenesis-related processes. Springer-Verlag, 2006 van Koningsbruggen Silvana Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut Straasheijm Kirsten Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut Sterrenburg Ellen Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut de Graaf Natascha Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut Dauwerse Hans Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut Frants Rune Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut van der Maarel Silvère Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut Chromosoma Springer-Verlag 116/1(2007-02-01), 53-64 0009-5915 116:1<53 2007 116 412 https://doi.org/10.1007/s00412-006-0083-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00412-006-0083-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- van Koningsbruggen Silvana Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut NATIONALLICENCE 700 1- Straasheijm Kirsten Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut NATIONALLICENCE 700 1- Sterrenburg Ellen Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut NATIONALLICENCE 700 1- de Graaf Natascha Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut NATIONALLICENCE 700 1- Dauwerse Hans Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut NATIONALLICENCE 700 1- Frants Rune Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut NATIONALLICENCE 700 1- van der Maarel Silvère Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Bldg. 2; room S-03-042, Postal zone 5-3-P, P.O. Box 9600, 2300 RC, Leiden, Netherlands aut NATIONALLICENCE 773 0- Chromosoma Springer-Verlag 116/1(2007-02-01), 53-64 0009-5915 116:1<53 2007 116 412 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer