Genome-wide protein interaction screens reveal functional networks involving Sm-like proteins

A set of seven structurally related Sm proteins forms the core of the snRNP particles containing the spliceosomal U1, U2, U4 and U5 snRNAs, A search o f the genomic sequence of Saccharomyces cerevisiae has identified a number of open reading frames that potentially encode structurally similar protein s termed Lsm (Like Sm) proteins. With the aim of analysing all possible int eractions between the Lsm proteins and any protein encoded in the yeast gen ome, we performed exhaustive and iterative genomic two-hybrid screens, star ting with the Lsm proteins as baits. Indeed, extensive interactions amongst eight Lsm proteins were found that suggest the existence of a Lsm complex or complexes, These Lsm interactions apparently involve the conserved Sm do main that also mediates interactions between the Sm proteins. The screens a lso reveal functionally significant interactions with splicing factors, in particular with Prp4 and Prp24, compatible with genetic studies and with th e reported association of Lsm proteins with spliceosomal U6 and U4/U6 parti cles. In addition, interactions with proteins involved in mRNA turnover, su ch as Mrt1, Dcp1, Dcp2 and Xrn1, point to roles for Lsm complexes in distin ct RNA metabolic processes, that are confirmed in independent functional st udies. These results provide compelling evidence that two-hybrid screens yi eld functionally meaningful information about protein-protein interactions and can suggest functions for uncharacterized proteins, especially when the y are performed on a genome-wide scale. Copyright (C) 2000 John Wiley & Son s, Ltd.