Lsm10-KO Mouse

Lsm10, a Sm D1-like protein, is a crucial component of the U7 small nuclear ribonucleoprotein (snRNP). U7 snRNP functions in the 3'-end processing of replication-dependent histone mRNAs, a process essential for normal cell function and development. The unique Sm core structure of U7 snRNP, where Lsm10 and Lsm11 replace SmD1 and SmD2, is significant for U7 snRNP function and sub-cellular localization [3,4].

In Drosophila, mutations in Lsm10 disrupt normal histone pre-mRNA processing, leading to the production of poly(A)+ histone mRNA due to transcriptional read-through. Lsm10 protein fails to accumulate in Lsm11 mutants, suggesting Lsm10-Lsm11 dimers are precursors for U7 snRNP assembly. Also, in SMA mice, co-expression of U7-specific Lsm10 and Lsm11 enhances U7 snRNP assembly, corrects histone mRNA processing defects, and rescues neuromuscular pathology, including NMJ denervation, decreased synaptic transmission, and skeletal muscle atrophy [2,1].

In conclusion, Lsm10 is essential for histone pre-mRNA processing and the proper function of U7 snRNP. Studies in Drosophila and SMA mice models have revealed its significance in maintaining normal development and in neuromuscular junction integrity, providing insights into potential therapeutic strategies for diseases like spinal muscular atrophy.

References:

1. Tisdale, Sarah, Van Alstyne, Meaghan, Simon, Christian M, Mentis, George Z, Pellizzoni, Livio. . SMN controls neuromuscular junction integrity through U7 snRNP. In Cell reports, 40, 111393. doi:10.1016/j.celrep.2022.111393. https://pubmed.ncbi.nlm.nih.gov/36130491/

2. Godfrey, Ashley C, White, Anne E, Tatomer, Deirdre C, Marzluff, William F, Duronio, Robert J. 2009. The Drosophila U7 snRNP proteins Lsm10 and Lsm11 are required for histone pre-mRNA processing and play an essential role in development. In RNA (New York, N.Y.), 15, 1661-72. doi:10.1261/rna.1518009. https://pubmed.ncbi.nlm.nih.gov/19620235/

3. Pillai, R S, Will, C L, Lührmann, R, Schümperli, D, Müller, B. . Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein. In The EMBO journal, 20, 5470-9. doi:. https://pubmed.ncbi.nlm.nih.gov/11574479/

4. Schümperli, D, Pillai, R S. . The special Sm core structure of the U7 snRNP: far-reaching significance of a small nuclear ribonucleoprotein. In Cellular and molecular life sciences : CMLS, 61, 2560-70. doi:. https://pubmed.ncbi.nlm.nih.gov/15526162/