前体信使RNAs (pre-mRNAs) 被剪接体（它由五个被称为snRNPs的子复合物组成）和其他辅助因子处理。每个snRNP含有一个由7个成分构成的蛋白环结构和一个相关的RNA分子。施一公及同事获得了U6 snRNP的Lsm蛋白环在有和没有一个包含U6 snRNA的3′端的 RNA两种情况下的晶体结构。这些数据揭示了RNA末端的四个尿嘧啶是怎样被几个U6 Lsm蛋白识别的，也将这些相互作用与Sm蛋白在其他snRNPs中与RNA的接触区分了开来。
Splicing of precursor messenger RNA (pre-mRNA) in eukaryotic cells is carried out by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs) and a number of accessory factors and enzymes. Each snRNP contains a ring-shaped subcomplex of seven proteins and a specific RNA molecule. The U6 snRNP contains a unique heptameric Lsm protein complex, which specifically recognizes the U6 small nuclear RNA at its 3′ end. Here we report the crystal structures of the heptameric Lsm complex, both by itself and in complex with a 3′ fragment of U6 snRNA, at 2.8 Å resolution. Each of the seven Lsm proteins interacts with two neighbouring Lsm components to form a doughnut-shaped assembly, with the order Lsm3–2–8–4–7–5–6. The four uridine nucleotides at the 3′ end of U6 snRNA are modularly recognized by Lsm3, Lsm2, Lsm8 and Lsm4, with the uracil base specificity conferred by a highly conserved asparagine residue. The uracil base at the extreme 3′ end is sandwiched by His 36 and Arg 69 from Lsm3, through π–π and cation–π interactions, respectively. The distinctive end-recognition of U6 snRNA by the Lsm complex contrasts with RNA binding by the Sm complex in the other snRNPs. The structural features and associated biochemical analyses deepen mechanistic understanding of the U6 snRNP function in pre-mRNA splicing.