title: How to find the optimal partner--studies of snurportin 1 interactions with U snRNA 5' TMG-cap analogues containing modified 2-amino group of 7-methylguanosine.
abstract: Snurportin 1 is an adaptor protein that mediates the active nuclear import of uridine-rich small nuclear RNAs (U snRNA) by the importin-β receptor pathway. Its cellular activity influences the overall transport yield of small ribonucleoprotein complexes containing N(2),N(2),7-trimethylguanosine (TMG) capped U snRNA. So far little is still known about structural requirements related to molecular recognition of the trimethylguanosine moiety by snurportin in solution. Since these interactions are of a great biomedical importance, we synthesized a series of new 7-methylguanosine cap analogues with extended substituents at the exocyclic 2-amino group to gain a deeper insight into how the TMG-cap is adapted into the snurportin cap-binding pocket. Prepared chemical tools were applied in binding assays using emission spectroscopy. Surprisingly, our results revealed strict selectivity of snurportin towards the TMG-cap structure that relied mainly on its structural stiffness and compactness.
authors.affiliation: Faculty of Chemistry, University of Warsaw, 1 Pasteura St., 02-093 Warsaw, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Piecyk
authors.affiliation: Laboratory of Biological Physics, Institute of Physics, Polish Academy of Sciences, 32/46 Lotników Ave., 02-668 Warsaw, Poland; Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 93 Żwirki I Wigury St., 02-089 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Niedzwiecka
authors.affiliation: Centre of New Technologies, University of Warsaw, 2C Banacha St., 02-097 Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Ferenc-Mrozek
authors.affiliation: Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 93 Żwirki I Wigury St., 02-089 Warsaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Lukaszewicz
authors.affiliation: Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 93 Żwirki I Wigury St., 02-089 Warsaw, Poland; Centre of New Technologies, University of Warsaw, 2C Banacha St., 02-097 Warsaw, Poland.
authors.forename: Edward
authors.initials: E
authors.lastname: Darzynkiewicz
authors.affiliation: Faculty of Chemistry, University of Warsaw, 1 Pasteura St., 02-093 Warsaw, Poland; Department of Biochemistry, Second Faculty of Medicine, Medical University of Warsaw, 101 Zwirki & Wigury Str., 02-089 Warsaw, Poland. Electronic address: marzena@chem.uw.edu.pl.
authors.forename: Marzena
authors.initials: M
authors.lastname: Jankowska-Anyszka
mesh_terms: D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D039381:RNA Cap-Binding Proteins / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D039381:RNA Cap-Binding Proteins; D012342:RNA, Small Nuclear; D018160:Receptors, Cytoplasmic and Nuclear; C114090:SNUPN protein, human; D006151:Guanosine; C016578:7-methylguanosine
keywords: Molecular recognition; Protein–ligand binding; Snurportin 1; TMG-cap; U snRNA