Biomedical subjects

Elissa P Lei

Publications and source records attributed to Elissa P Lei.

6 recordsLinked to original sources

PubMed2006

RNA interference machinery influences the nuclear organization of a chromatin insulator.

RNA interference (RNAi) is a conserved silencing mechanism that can act through alteration of chromatin structure. Chromatin insulators promote higher-order nuclear organization, thereby establishing DNA domains subject to distinct transcriptional controls. We present evidence for a functional relationship between RNAi and the gypsy insulator of D. melanogaster. Insulator activity is decreased when Argonaute genes required for RNAi are mutated, and insulator function is improved when the levels of the Rm62 helicase, involved in double-stranded RNA (dsRNA)-mediated silencing and heterochromatin formation, are reduced. Rm62 interacts physically with the DNA-binding insulator protein CP190 in an RNA-dependent manner. Finally, reduction of Rm62 levels results in marked nuclear reorganization of a compromised insulator. These results suggest that the RNAi machinery acts as a modulator of nuclear architecture capable of effecting global changes in gene expression.

Animals↗

PubMed2006

A long-distance relationship between RNAi and Polycomb.

RNA interference (RNAi) pathways can result in sequence-specific transcriptional gene silencing on the level of chromatin. In this issue of Cell, Grimaud et al. (2006) reveal that the RNAi machinery is required for long-distance physical interactions between chromosomes mediated by the Polycomb repressive complex. These results suggest that the RNAi machinery may regulate higher-order nuclear organization.

Cell Nucleus↗

PubMed2004

The centrosomal protein CP190 is a component of the gypsy chromatin insulator.

Chromatin insulators, or boundary elements, affect promoter-enhancer interactions and buffer transgenes from position effects. The gypsy insulator of Drosophila is bound by a protein complex with two characterized components, the zinc finger protein Suppressor of Hairy-wing [Su(Hw)] and Mod(mdg4)2.2, which is one of the multiple spliced variants encoded by the modifier of mdg4 [mod(mdg4)] gene. A genetic screen for dominant enhancers of the mod(mdg4) phenotype identified the Centrosomal Protein 190 (CP190) as an essential constituent of the gypsy insulator. The function of the centrosome is not affected in CP190 mutants whereas gypsy insulator activity is impaired. CP190 associates physically with both Su(Hw) and Mod(mdg4)2.2 and colocalizes with both proteins on polytene chromosomes. CP190 does not interact directly with insulator sequences present in the gypsy retrotransposon but binds to a previously characterized endogenous insulator, and it is necessary for the formation of insulator bodies. The results suggest that endogenous gypsy insulators contain binding sites for CP190, which is essential for insulator function, and may or may not contain binding sites for Su(Hw) and Mod(mdg4)2.2.

Alleles↗

PubMed2003

Sac3 is an mRNA export factor that localizes to cytoplasmic fibrils of nuclear pore complex.

In eukaryotes, mRNAs are transcribed in the nucleus and exported to the cytoplasm for translation to occur. Messenger RNAs complexed with proteins referred to as ribonucleoparticles are recognized for nuclear export in part by association with Mex67, a key Saccharomyces cerevisiae mRNA export factor and homolog of human TAP/NXF1. Mex67, along with its cofactor Mtr2, is thought to promote ribonucleoparticle translocation by interacting directly with components of the nuclear pore complex (NPC). Herein, we show that the nuclear pore-associated protein Sac3 functions in mRNA export. Using a mutant allele of MTR2 as a starting point, we have identified a mutation in SAC3 in a screen for synthetic lethal interactors. Loss of function of SAC3 causes a strong nuclear accumulation of mRNA and synthetic lethality with a number of mRNA export mutants. Furthermore, Sac3 can be coimmunoprecipitated with Mex67, Mtr2, and other factors involved in mRNA export. Immunoelectron microscopy analysis shows that Sac3 localizes exclusively to cytoplasmic fibrils of the NPC. Finally, Mex67 accumulates at the nuclear rim when SAC3 is mutated, suggesting that Sac3 functions in Mex67 translocation through the NPC.

Biological Transport↗

PubMed2002

Intron status and 3'-end formation control cotranscriptional export of mRNA.

Messenger RNA export factors are recruited to genes in a transcription-dependent manner. To ascertain the mechanism of this process, we show that RNA polymerase II transcription is sufficient to recruit the Saccharomyces cerevisiae hnRNP protein Npl3 to a gene independent of RNA sequence. In contrast, the cotranscriptional recruitment of the RNA-binding protein Yra1 is dependent on pre-mRNA processing. Yra1 associates with introns of intron-containing genes in a splicing-dependent manner. Conversely, Yra1 recruitment to genes without introns is not dependent on splicing. Finally, 3'-end formation is required for Yra1 recruitment to genes regardless of intron status.

Heterogeneous-Nuclear Ribonucleoproteins↗

PubMed2002

Protein and RNA export from the nucleus.

The presence of the nuclear envelope necessitates the movement of proteins and RNAs between the nucleus and the cytoplasm. Elaborate cellular machinery exists to promote the nuclear transport of macromolecules. Recent advances in the field have illuminated our comprehension of both nuclear import and export as powerful means of gene regulation. As our appreciation of the importance of the process has grown, its study has matured, moving beyond the single cell to the entire organism. This review discusses basic mechanisms and regulation of protein, mRNA, and ribosome export with an emphasis on developmental examples.

Active Transport, Cell Nucleus↗