Figure 3. U6 snRNP metabolism requires Lsm2-8. U6 snRNA is transcribed in the nucleus by RNA polymerase III and terminates in four uridine residues, which recruit the La RNA-binding protein.⁴⁸ The U tract is extended by U6 TUTase leading to exchange of La for Lsm2-8.^49,52 The U-tract is then trimmed to five residues by Mpn1 and consequently terminates in a 2’,3′ cyclic phosphate.^50,51 Lsm binding allows association of Prp24/p110 to generate mature U6 snRNA.⁹⁹ Lsm facilitates annealing of U4 and U6 and the complex enters the spliceosome. Subsequent rearrangements allow U6 to interact with U2 and the pre-mRNA and Lsm2-8 and p110 are then ejected prior to the first step of splicing.⁸⁸ After splicing, U6 is released in a form that is accessible to various RNA-modifying enzymes. U6 snRNP must then be reassembled prior to being re-used. Lsm2-8 and the U6 TUTase may participate in a quality control mechanism to ensure the U-tract remains intact.