High impact information on MLP1

• When overall pre-mRNA levels are increased by deletion of RRP6, a nuclear exosome component, MLP1 deletion augments leakage of only the intron-containing portion of mRNAs [1].
• The Mlp1-dependent leakage of intron-containing RNAs is increased in presence of ts-prp18 delta, a splicing mutant [1].
• Furthermore, double deletion of MLP1 and MLP2 disrupts the clustering of perinuclear telomeres and releases telomeric gene repression [2].
• High-resolution mapping of association of chromosome III with Mlp1 revealed alpha-factor-dependent determinants of nuclear pore association, including origins of replication, specific intergenic regions, and the 3' ends of transcriptionally activated genes [3].
• The loss of Mlp1p/Mlp2p, two TPR-like proteins attached to nuclear pores, rescues LacZ mRNA levels and increases their appearance in the cytoplasm, without restoring bulk poly(A)+ RNA export [4].

Biological context of MLP1

• Remarkably, cells harboring a double deletion of MLP1 and MLP2 were viable, although they showed a slower net rate of active nuclear import and faster passive efflux of a reporter protein [5].
• Cells lacking MLP1 and GRX5 are hypersensitive to oxidative stress caused by external agents and exhibit increased protein oxidation in relation to single mutants [6].
• Overexpression of MLP1 suppresses the caffeine-sensitive phenotype of the bck1 delta mutation [7].
• Mutants bearing disruptions of the MLP1 gene were viable, but more sensitive to ultraviolet light than wild-type strains, suggesting an involvement of MLP1 in DNA repair [8].
• The MLP1 gene was mapped to chromosome 11, 25 cM from met1 [8].

Anatomical context of MLP1

• It has been reported that two large coiled-coil proteins of the nuclear envelope, myosin-like proteins 1 and 2, play direct roles in anchoring yeast telomeres to the nuclear periphery, thereby creating a subcompartment enriched for Sir proteins [9].
• Several have features reminiscent of cytoskeleton or motor elements (keratin-like, myosin-like) and several others have characteristics of proteins which interact with DNA (extremely basic, b-Zip structure and/or acidic domains) [10].
• Here we show that nuclear-pore-complex extensions formed by the conserved TPR homologues Mlp1 and Mlp2 are responsible for the structural and functional organization of perinuclear chromatin [2].
• In mouse epithelial cells the yeast anti-MLP1 antibodies stained the nucleus [8].
• These findings suggest that myosin or a myosin-like protein plays a key role in insulin-regulated movement of GLUT4 to the plasma membrane in rat adipocytes [11].

Physical interactions of MLP1

• We propose a model where Mlp1p acts as a checkpoint at the nuclear pore by interacting with export-competent ribonucleoprotein complexes through its C-terminal globular domain [12].

Other interactions of MLP1

• Myosin-like proteins 1 and 2 are not required for silencing or telomere anchoring, but act in the Tel1 pathway of telomere length control [9].
• One of these is MLP1, which codes for a homologue of the Slt2 kinase [6].
• In addition, our experiments reveal that the C-terminal domain of Mlp1p is both necessary and sufficient to cause accumulation of poly(A) RNA and Nab2p in the nucleus [12].
• We identified a yeast two-hybrid interaction between the C-terminal globular domain of Mlp1p and Nab2p, a shuttling heterogeneous nuclear ribonucleoprotein that is required for mRNA export [12].
• The phenotype of the TPM1 disrupted cells is very similar to that of a conditional mutation in the MYO2 gene, which encodes a myosin-like protein (Johnston, G. C., J. A. Prendergast, and R. A. Singer. 1991. J. Cell Biol. 113:539-551) [13].

References