27 research outputs found
Comprehensive splice-site analysis using comparative genomics
We have collected over half a million splice sites from five speciesâHomo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thalianaâand classified them into four subtypes: U2-type GTâAG and GCâAG and U12-type GTâAG and ATâAC. We have also found new examples of rare splice-site categories, such as U12-type introns without canonical borders, and U2-dependent ATâAC introns. The splice-site sequences and several tools to explore them are available on a public website (SpliceRack). For the U12-type introns, we find several features conserved across species, as well as a clustering of these introns on genes. Using the information content of the splice-site motifs, and the phylogenetic distance between them, we identify: (i) a higher degree of conservation in the exonic portion of the U2-type splice sites in more complex organisms; (ii) conservation of exonic nucleotides for U12-type splice sites; (iii) divergent evolution of C.elegans 3âČ splice sites (3âČss) and (iv) distinct evolutionary histories of 5âČ and 3âČss. Our study proves that the identification of broad patterns in naturally-occurring splice sites, through the analysis of genomic datasets, provides mechanistic and evolutionary insights into pre-mRNA splicing
Galaxy bulges and their massive black holes: a review
With references to both key and oft-forgotten pioneering works, this article
starts by presenting a review into how we came to believe in the existence of
massive black holes at the centres of galaxies. It then presents the historical
development of the near-linear (black hole)-(host spheroid) mass relation,
before explaining why this has recently been dramatically revised. Past
disagreement over the slope of the (black hole)-(velocity dispersion) relation
is also explained, and the discovery of sub-structure within the (black
hole)-(velocity dispersion) diagram is discussed. As the search for the
fundamental connection between massive black holes and their host galaxies
continues, the competing array of additional black hole mass scaling relations
for samples of predominantly inactive galaxies are presented.Comment: Invited (15 Feb. 2014) review article (submitted 16 Nov. 2014). 590
references, 9 figures, 25 pages in emulateApJ format. To appear in "Galactic
Bulges", E. Laurikainen, R.F. Peletier, and D.A. Gadotti (eds.), Springer
Publishin
Global Boundary Stratotype Section and Point (GSSP) for the Anthropocene Series: Where and how to look for potential candidates
International audienc
A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy.
A mutation equivalent to P102L in the human PrP gene, associated with Gerstmann-Straussler syndrome (GSS), has been introduced into the murine PrP gene by gene targeting. Mice homozygous for this mutation (101LL) showed no spontaneous transmissible spongiform encephalopathy (TSE) disease, but had incubation times dramatically different from wild-type mice following inoculation with different TSE sources. Inoculation with GSS produced disease in 101LL mice in 288 days. Disease was transmitted from these mice to both wild-type (226 days) and 101LL mice (148 days). In contrast, 101LL mice infected with ME7 had prolonged incubation times (338 days) compared with wild-type mice (161 days). The 101L mutation does not, therefore, produce any spontaneous genetic disease in mice but significantly alters the incubation time of TSE infection. Additionally, a rapid TSE transmission was demonstrated despite extremely low levels of disease-associated PrP
States Decrease Their Required Secondary Transition Planning Age: Federal Policy Must Change
Minimise transmission risk of CJD and vCJD in healthcare settings. Report on the Prevention of CJD and vCJD by Advisory Committee on Dangerous Pathogens' Transmission Spongiform Encephalopathy (ACDP TSE) Subgroup.
An LKB1 AT-AC intron mutation causes Peutz-Jeghers syndrome via splicing at noncanonical cryptic splice sites
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder associated with gastrointestinal polyposis and an increased cancer risk. PJS is caused by germline mutations in the tumor suppressor gene LKB1. One such mutation, IVS2+1A>G, alters the second intron 5' splice site, which has sequence features of a U12-type AT-AC intron. We report that in patients, LKB1 RNA splicing occurs from the mutated 5' splice site to several cryptic, noncanonical 3' splice sites immediately adjacent to the normal 3' splice site. In vitro splicing analysis demonstrates that this aberrant splicing is mediated by the U12-dependent spliceosome. The results indicate that the minor spliceosome can use a variety of 3' splice site sequences to pair to a given 5' splice site, albeit with tight constraints for maintaining the 3' splice site position. The unusual splicing defect associated with this PJS-causing mutation uncovers differences in splice-site recognition between the major and minor pre-mRNA splicing pathways