title: Restraint of the G2/M transition by the SR/RRM family mRNA shuttling binding protein SNXAHRB1 in Aspergillus nidulans.
abstract: Control of the eukaryotic G2/M transition by CDC2/CYCLINB is tightly regulated by protein-protein interactions, protein phosphorylations, and nuclear localization of CDC2/CYCLINB. We previously reported a screen, in Aspergillus nidulans, for extragenic suppressors of nimX2(cdc2) that resulted in the identification of the cold-sensitive snxA1 mutation. We demonstrate here that snxA1 suppresses defects in regulators of the CDK1 mitotic induction pathway, including nimX2(cdc) (2), nimE6(cyclinB), and nimT23(cdc) (25), but does not suppress G2-arresting nimA1/nimA5 mutations, the S-arresting nimE10(cyclinB) mutation, or three other G1/S phase mutations. snxA encodes the A. nidulans homolog of Saccharomyces cerevisiae Hrb1/Gbp2; nonessential shuttling messenger RNA (mRNA)-binding proteins belonging to the serine-arginine-rich (SR) and RNA recognition motif (RRM) protein family; and human heterogeneous ribonucleoprotein-M, a spliceosomal component involved in pre-mRNA processing and alternative splicing. snxA(Hrb) (1) is nonessential, its deletion phenocopies the snxA1 mutation, and its overexpression rescues snxA1 and ΔsnxA mutant phenotypes. snxA1 and a second allele isolated in this study, snxA2, are hypomorphic mutations that result from decreased transcript and protein levels, suggesting that snxA acts normally to restrain cell cycle progression. SNXA(HRB1) is predominantly nuclear, but is not retained in the nucleus during the partially closed mitosis of A. nidulans. We show that the snxA1 mutation does not suppress nimX2 by altering NIMX2(CDC2)/NIME(CYCLINB) kinase activity and that snxA1 or ΔsnxA alter localization patterns of NIME(CYCLINB) at the restrictive temperatures for snxA1 and nimX2. Together, these findings suggest a novel and previously unreported role of an SR/RRM family protein in cell cycle regulation, specifically in control of the CDK1 mitotic induction pathway.
authors.affiliation: Biology Department, Gettysburg College, Gettysburg, Pennsylvania 17325 sjames@gettysburg.edu mcguisl@millsaps.edu.
authors.forename: Steven W
authors.initials: SW
authors.lastname: James
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Travis
authors.initials: T
authors.lastname: Banta
authors.affiliation: Biology Department, Gettysburg College, Gettysburg, Pennsylvania 17325.
authors.forename: James
authors.initials: J
authors.lastname: Barra
authors.affiliation: Biology Department, Gettysburg College, Gettysburg, Pennsylvania 17325.
authors.forename: Lorela
authors.initials: L
authors.lastname: Ciraku
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Clifford
authors.initials: C
authors.lastname: Coile
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Zach
authors.initials: Z
authors.lastname: Cuda
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Ryan
authors.initials: R
authors.lastname: Day
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Cheshil
authors.initials: C
authors.lastname: Dixit
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Steven
authors.initials: S
authors.lastname: Eastlack
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Anh
authors.initials: A
authors.lastname: Giang
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: James
authors.initials: J
authors.lastname: Goode
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Alexis
authors.initials: A
authors.lastname: Guice
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Yulon
authors.initials: Y
authors.lastname: Huff
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Sara
authors.initials: S
authors.lastname: Humbert
authors.affiliation: Biology Department, Gettysburg College, Gettysburg, Pennsylvania 17325.
authors.forename: Christina
authors.initials: C
authors.lastname: Kelliher
authors.affiliation: Biology Department, Gettysburg College, Gettysburg, Pennsylvania 17325.
authors.forename: Julie
authors.initials: J
authors.lastname: Kobie
authors.affiliation: Biology Department, Gettysburg College, Gettysburg, Pennsylvania 17325.
authors.forename: Emily
authors.initials: E
authors.lastname: Kohlbrenner
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Faustin
authors.initials: F
authors.lastname: Mwambutsa
authors.affiliation: Biology Department, Gettysburg College, Gettysburg, Pennsylvania 17325.
authors.forename: Amanda
authors.initials: A
authors.lastname: Orzechowski
authors.affiliation: Biology Department, Gettysburg College, Gettysburg, Pennsylvania 17325.
authors.forename: Kristin
authors.initials: K
authors.lastname: Shingler
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210.
authors.forename: Casey
authors.initials: C
authors.lastname: Spell
authors.affiliation: Biology Department, Millsaps College, Jackson, Mississippi 39210 sjames@gettysburg.edu mcguisl@millsaps.edu.
authors.forename: Sarah Lea
authors.initials: SL
authors.lastname: Anglin
mesh_terms: D001233:Aspergillus nidulans / Q000166:cytology* / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase; D015870:Gene Expression; D007399:Interphase; D009154:Mutation; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D019926:Cyclin B; D005656:Fungal Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016203:CDC2 Protein Kinase
keywords: CDC2/CYCLINB; G2/M transition; Hrb1/Gbp2; SR/RRM; cell cycle
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