Tfip11, or tuftelin-interacting protein 11, is a protein component of the spliceosome complex. It is essential for processes like spliceosome disassembly, U6 snRNA modification, and U4/U6.U5 tri-snRNP assembly, which are crucial for pre-mRNA splicing fidelity. It also has a role in replication fork reversal, an important protective mechanism against replication stress, thereby contributing to genome stability. Its study in genetic models can help understand its complex functions [1,2,3].

Loss-of-function experiments show that loss of either TFIP11 or BLM leads to abnormal accumulation of the other at stalled forks, impairing RAD51-mediated fork reversal and slowing. This sensitizes cells to replication-stress-inducing agents and enhances chromosomal instability, revealing its role in modulating the activities of BLM and RAD51 at stalled forks and thus genome integrity [1]. Also, TFIP11 knockdown reduces the association of U6 snRNA with fibrillarin and associated snoRNAs, altering U6 2'-O-methylation, which impacts spliceosome assembly and splicing fidelity [3].

In conclusion, Tfip11 is vital for pre-mRNA splicing and genome stability. Studies using gene knockout models have revealed its role in replication fork-related processes, potentially contributing to understanding chromosomal instability-related diseases, and in U6 snRNA modification-related splicing processes, providing insights into disorders associated with abnormal splicing.