title: Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL.
abstract: Differentiation of memory cells involves DNA-sequence changes in B lymphocytes but is less clearly defined in T cells. RNA rearrangement is identified here as a key event in memory T cell differentiation by analysis of a mouse mutation that altered the proportions of naive and memory T cells and crippled the process of Ptprc exon silencing needed to generate CD45RO in memory T cells. A single substitution in a memory-induced RNA-binding protein, hnRNPLL, destabilized an RNA-recognition domain that bound with micromolar affinity to RNA containing the Ptprc exon-silencing sequence. Hnrpll mutation selectively diminished T cell accumulation in peripheral lymphoid tissues but not proliferation. Exon-array analysis of Hnrpll mutant naive and memory T cells revealed an extensive program of alternative mRNA splicing in memory T cells, coordinated by hnRNPLL. A remarkable overlap with alternative splicing in neural tissues may reflect a co-opted strategy for diversifying memory T cells.
authors.affiliation: John Curtin School of Medical Research, Australian Phenomics Facility, Australian National University, Canberra ACT 0200, Australia.
authors.forename: Zuopeng
authors.initials: Z
authors.lastname: Wu
authors.forename: Xinying
authors.initials: X
authors.lastname: Jia
authors.forename: Laura
authors.initials: L
authors.lastname: de la Cruz
authors.forename: Xun-Cheng
authors.initials: XC
authors.lastname: Su
authors.forename: Bruz
authors.initials: B
authors.lastname: Marzolf
authors.forename: Pamela
authors.initials: P
authors.lastname: Troisch
authors.forename: Daniel
authors.initials: D
authors.lastname: Zak
authors.forename: Adam
authors.initials: A
authors.lastname: Hamilton
authors.forename: Belinda
authors.initials: B
authors.lastname: Whittle
authors.forename: Di
authors.initials: D
authors.lastname: Yu
authors.forename: Daniel
authors.initials: D
authors.lastname: Sheahan
authors.forename: Edward
authors.initials: E
authors.lastname: Bertram
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.forename: Gottfried
authors.initials: G
authors.lastname: Otting
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: Gerard F
authors.initials: GF
authors.lastname: Hoyne
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D005091:Exons / Q000235:genetics*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007156:Immunologic Memory / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012313:RNA / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D020033:Protein Isoforms; C534662:hnRNPLL protein, mouse; D012313:RNA; D017493:Leukocyte Common Antigens