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

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55 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

Wu, Z., Jia, X., de la Cruz, L., Su, X-C., Marzolf, B., Troisch, P., Zak, D., Hamilton, A., Whittle, B., Yu, D., Sheahan, D., Bertram, E., Aderem, A., Otting, G., Goodnow, C. C., & Hoyne, G. F. (2008). Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL. Immunity, 29(6), 863 - 875. https://doi.org/10.1016/j.immuni.2008.11.004