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Biomedical subjects

E Jan

Publications and source records attributed to E Jan.

6 recordsLinked to original sources
PubMed2005

Takeover of host ribosomes by divergent IRES elements.

The ribosome is the macromolecular machinery in the host cell for which all viruses have to compete. Early in infection, the viral mRNAs have to compete with the host for both the ribosomes and for the limited pool of eukaryotic initiation factors that are needed to facilitate the recruitment of ribosomes to both viral and cellular mRNAs. To circumvent this competition, certain viruses have evolved to recruit ribosomes to IRESs (internal ribosome entry sites), highly specialized RNA elements that are located at the 5'-end of the viral genomes. Here, we discuss how divergent IRES elements can recruit ribosomes and start protein synthesis with only a minimal set of eukaryotic translation initiation factors, and how this mode of translation initiation aids viral gene amplification during early onset of innate immune responses.

Animals↗
PubMed2003

Interinstitutional pathology consultations. A reassessment.

We retrospectively determined the clinical impact of 1,000 randomly selected interinstitutional pathology consultations (IPCs). An IPC included all specimens from the patient. IPCs were classified as concordant or discordant with the original diagnosis. Discordant IPCs were classified as having a clinical impact or no impact. Discordant IPCs owing to interpretation differences were subclassified further. The IPCs included 1,522 specimens (1,204 histology, 318 cytology); 923 (92.3%) were concordant, 9 (0.9%) indeterminate, and 68 (6.8%) discordant (clinical impact, 37; no impact, 31). Reasons for discordant IPCs were interpretation differences, 45; additional sectioning, 7; ancillary testing, 1; clerical error, 5; or a combination, 10. Reasons for 26 discordant IPCs with clinical impact owing to interpretation differences were overdiagnosis, 11; tumor subtype change, 4; stage change, 4; underdiagnosis, 3; resection margin status change, 2; undergrading, 1; and understaging with resection margin status change, 1. IPC may identify diagnostic discrepancies that impact management for some patients. The prevalence of a clinical impact of IPC on management varies according to body site. Mandatory IPC does ensure identification of clinically significant diagnostic discrepancies; targeted IPC by body site or specimen type may represent an alternative strategy after further data accumulation. Discordant IPCs may be due to factors other than interpretation difference.

Humans↗
PubMed1999

The STAR protein QKI-6 is a translational repressor.

The signal transduction and activation of RNA (STAR) family of RNA-binding proteins, whose members are evolutionarily conserved from yeast to humans, are important for a number of developmental decisions. For example, in the mouse, quaking proteins (QKI-5, QKI-6, and QKI-7) are essential for embryogenesis and myelination, whereas a closely related protein in Caenorhabditis elegans, germline defective-1 (GLD-1), is necessary for germ-line development. Recently, GLD-1 was found to be a translational repressor that acts through regulatory elements, called TGEs (for tra-2 and GLI elements), present in the 3' untranslated region of the sex-determining gene tra-2. This gene promotes female development, and repression of tra-2 translation by TGEs is necessary for the male cell fates. The finding that GLD-1 inhibits tra-2 translation raises the possibility that other STAR family members act by a similar mechanism to control gene activity. Here we demonstrate, both in vitro and in vivo, that QKI-6 functions in the same manner as GLD-1 and can specifically bind to TGEs to repress translation of reporter constructs containing TGEs. In addition, expression of QKI-6 in C. elegans wild-type hermaphrodites or in hermaphrodites that are partially masculinized by a loss-of-function mutation in the sex-determining gene tra-3 results in masculinization of somatic tissues, consistent with QKI-6 repressing the activity of tra-2. These results strongly suggest that QKI-6 may control gene activity by operating through TGEs to regulate translation. In addition, our data support the hypothesis that other STAR family members may also be TGE-dependent translational regulators.

3' Untranslated Regions↗
PubMed1999

The STAR protein, GLD-1, is a translational regulator of sexual identity in Caenorhabditis elegans.

The Caenorhabditis elegans sex determination gene, tra-2, is translationally regulated by elements in the 3'-untranslated region called TGEs. TGEs govern the translation of mRNAs in both invertebrates and vertebrates, indicating that this is a highly conserved mechanism for controlling gene activity. A factor called DRF, found in worm extracts binds the TGEs and may be a repressor of translation. Using the yeast three-hybrid screen and RNA gel shift analysis, we have found that the protein GLD-1, a germline-specific protein and a member of the STAR family of RNA-binding proteins, specifically binds to the TGEs. GLD-1 is essential for oogenesis, and is also necessary for spermatogenesis and inhibition of germ cell proliferation. Several lines of evidence demonstrate that GLD-1 is a translational repressor acting through the TGEs to repress tra-2 translation. GLD-1 can repress the translation of reporter RNAs via the TGEs both in vitro and in vivo, and is required to maintain low TRA-2A protein levels in the germline. Genetic analysis indicates that GLD-1 acts upstream of the TGE control. Finally, we show that endogenous GLD-1 is a component of DRF. The conservation of the TGE control and the STAR family suggests that at least a subset of STAR proteins may work through the TGEs to control translation.

Animals↗
PubMed1997

Conservation of the C.elegans tra-2 3'UTR translational control.

The Caenorhabditis elegans sex-determination gene, tra-2, is translationally regulated by two 28 nt elements (DREs) located in the 3'UTR that bind a factor called DRF. This regulation requires the laf-1 gene activity. We demonstrate that the nematode Caenorhabditis briggsae tra-2 gene and the human oncogene GLI are translationally regulated by elements that are functionally equivalent to DREs. Here, we rename the DREs to TGEs (tra-2 and GLI elements). Similarly to the C.elegans tra-2 TGEs, the C.briggsae tra-2 and GLI TGEs repress translation of a reporter transgene in a laf-1 dependent manner. Furthermore, they regulate poly(A) tail length and bind DRF. We also find that the C.elegans TGEs control translation and poly(A) tail length in C.briggsae and rodent cells. Moreover, these same organisms contain a factor that specifically associates with the C.elegans TGEs. These findings are consistent with the TGE control being present in C.briggsae and rodent cells. Three lines of evidence indicate that C.briggsae tra-2 and GLI are translationally controlled in vivo by TGEs. First, like C.elegans tra-2 TGEs, the C.briggsae tra-2 and GLI TGEs control translation and poly(A) tail lengths in C.briggsae and rodent cells, respectively. Second, the same factor in C.briggsae and mammalian cells that binds to the C.elegans tra-2 TGEs binds the C.briggsae tra-2 and GLI TGEs. Third, deletion of the GLI TGE increases GLI's ability to transform cells. These findings suggest that TGE control is conserved and regulates the expression of other mRNAs.

Amino Acid Sequence↗