Figure 3. thunder Is a Missense Mutation in the RNA-Recognition Motif of hnRNPLL.

(A) Meiotic mapping of thunder to a 2.1 Mb interval derived from the B6-thunder strain.

(B) Candidate RNA-regulating genes within the interval.

(C) T→A substitution in thunder mRNA nucleotide 684, codon 136.

(D) Predicted domains of the hnRNPLL and hnRNPL proteins. Abbreviations are as follows: RRM, RNA recognition motif domain; PR, proline rich domain.

(E) Amino acid sequence alignment of the hnRNPLL RRM1 domain from different vertebrate species and with corresponding RRM domains from hnRNPL and PTB1. Gold boxes denote two RNP motifs that form a central binding site for RNA, with key RNA contacts on H and Q residues. The regular secondary-structure elements in the RRM1 domain of hnRNPLL are indicated at the top.

(F) thu/thu T lymphoblasts were transduced with a bicistronic retroviral vector containing WT Hnrpll cDNA and EGFP or containing WT EGFP alone. Flow-cytometric staining for CD45RC is shown gated on GFP⁺ cells (gray histograms) compared with nontransduced GFP° cells in the same culture (open histograms), showing correction of CD45RC silencing by the WT cDNA.

(G) Relative mRNA abundance of Hnrpll (upper panel) and Hnrpl (lower panel) in WT naive and memory CD4⁺ and CD8⁺ T cells measured by qRT-PCR, normalized to Ube2D1. Columns indicate means, and error bars indicate standard deviations from n = 3 mice.