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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.

journal_name

Immunity

journal_title

Immunity

authors

Wu Z,Jia X,de la Cruz L,Su XC,Marzolf B,Troisch P,Zak D,Hamilton A,Whittle B,Yu D,Sheahan D,Bertram E,Aderem A,Otting G,Goodnow CC,Hoyne GF

doi

10.1016/j.immuni.2008.11.004

subject

Has Abstract

pub_date

2008-12-19 00:00:00

pages

863-75

issue

6

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(08)00508-6

journal_volume

29

pub_type

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