Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL

Zuopeng Wu, Xinying Jia, Laura de la Cruz, Xu-Cheng Su, Bruz Marzolf, Pamela Troisch, Daniel Zak, Adam Hamilton, Belinda Whittle, Di Yu, Daniel Sheahan, Edward Bertram, Alan Aderem, Gottfried Otting, Christopher C Goodnow, Gerard F Hoyne

Research output: Contribution to journalArticleResearchpeer-review

67 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)863 - 875
Number of pages13
JournalImmunity
Volume29
Issue number6
DOIs
Publication statusPublished - 2008
Externally publishedYes

Cite this