Abstract:
:The fission yeast telomerase RNA (TER1) precursor harbors an intron immediately downstream from its mature 3' end. Unlike most introns, which are removed from precursor RNAs by the spliceosome in two sequential but tightly coupled transesterification reactions, TER1 only undergoes the first cleavage reaction during telomerase RNA maturation. The mechanism underlying spliceosome-mediated 3' end processing has remained unclear. We now demonstrate that a strong branch site (BS), a long distance to the 3' splice site (3' SS), and a weak polypyrimidine (Py) tract act synergistically to attenuate the transition from the first to the second step of splicing. The observation that a strong BS antagonizes the second step of splicing in the context of TER1 suggests that the BS-U2 snRNA interaction is disrupted after the first step and thus much earlier than previously thought. The slow transition from first to second step triggers the Prp22 DExD/H-box helicase-dependent rejection of the cleaved products and Prp43-dependent "discard" of the splicing intermediates. Our findings explain how the spliceosome can function in 3' end processing and provide new insights into the mechanism of splicing.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Kannan R,Hartnett S,Voelker RB,Berglund JA,Staley JP,Baumann Pdoi
10.1101/gad.212738.112subject
Has Abstractpub_date
2013-03-15 00:00:00pages
627-38issue
6eissn
0890-9369issn
1549-5477pii
gad.212738.112journal_volume
27pub_type
杂志文章abstract::We have analyzed pre-mRNA splicing in yeast extracts immunodepleted of the PRP18 protein. We find that while the first step of splicing (cleavage at the 5' splice site, and generation of the exon 1 and lariat intermediates) is unaffected by the absence of PRP18, the second step of splicing (excision of the lariat intr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.2.320
更新日期:1993-02-01 00:00:00
abstract::PBAF and BAF are two chromatin-remodeling complexes of the SWI/SNF family essential for mammalian transcription and development. Although these complexes share eight identical subunits, only PBAF can facilitate transcriptional activation by nuclear receptors in vitro. Here we show that these complexes have selectivity...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1323805
更新日期:2005-07-15 00:00:00
abstract::Abcission, the natural shedding of leaves, flowers and fruits, is a fundamental component of plant development. Abscission is a highly regulated process that occurs at distinct zones of cells that undergo enlargement and subsequent separation. Although some components of abscission, including accumulation of the hormo...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::Noncoding RNA regulators have been implicated in almost all imaginable cellular processes. Here we review how regulatory small RNAs such as Spot42, SgrS, GlmY, and GlmZ and a cis-encoded ribozyme in glmS mRNA control sugar metabolism. Besides discussing the physiological implications, we show how the study of these mo...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1717808
更新日期:2008-11-01 00:00:00
abstract::This paper examines ovarian transcription of the divergently oriented yolk protein genes 1 and 2 (yp1 and yp2) of Drosophila melanogaster. We report germ line transformation results demonstrating that yp1 and yp2 are transcribed in the same subpopulations of ovarian follicle cells. Our results show that this expressio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.613
更新日期:1990-04-01 00:00:00
abstract::MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.17221311
更新日期:2011-10-15 00:00:00
abstract::The P family of transposable elements in Drosophila transpose by a cut-and-paste mechanism involving double-strand gap repair. We report here that a Drosophila mutagen-sensitive mutant, mus3O9, contains a mutation in IRBP (inverted repeat binding protein), the Drosophila homolog of the mammalian Ku p70 gene. We show t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.8.921
更新日期:1996-04-15 00:00:00
abstract::Two independent two-dimensional (2D) gel methods were used to map an origin of replication that is developmentally regulated by the steroid hormone ecdysone, namely an origin for DNA puff amplification in the fungus fly Sciara coprophila. Initiation of replication was found to occur within a small region of no larger ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.6.1072
更新日期:1993-06-01 00:00:00
abstract::The dihydrofolate reductase (DHFR) and 2BE2121 genes in the Chinese hamster are convergently transcribed in late G1 and ea ly S phase, and bracket an early-firing origin of replication that consists of a 55-kb zone of potential initiation sites. To test whether transcription through the DHFR gene is required to activa...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1171404
更新日期:2004-02-15 00:00:00
abstract::The Drosophila brain tumor (brat) gene encodes a member of the conserved NHL family of proteins, which appear to regulate differentiation and growth in a variety of organisms. One of the founding family members, Caenorhabditis elegans LIN-41, is thought to control posttranscriptional gene expression. However, the mech...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.870801
更新日期:2001-03-15 00:00:00
abstract::We have shown that Wnt signals are necessary and sufficient for neural crest cells to adopt pigment cell fates. nacre, a zebrafish homolog of MITF, is required for pigment cell differentiation. We isolated a promoter region of nacre that contains Tcf/Lef binding sites, which can mediate Wnt responsiveness. This promot...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-01-15 00:00:00
abstract::The human RNA polymerase II (RNAPII)-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases, including cancer. However, its involvement in breast cancer awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr9, the key scaffold...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.268722.115
更新日期:2015-10-15 00:00:00
abstract::Regions on the surface of human TATA-box binding protein (TBP) required for activated transcription in vivo were defined by construction of a library of 89 surface residue mutants with radical substitutions that were assayed for their ability to support activated transcription in vivo, basal transcription in vitro, an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.19.2491
更新日期:1996-10-01 00:00:00
abstract::SNF2 chromatin-remodeling ATPases play an important role in ensuring proper development in higher eukaryotes by controlling accessibility of cis-regulatory DNA regions to transcription factors and to the transcriptional machinery. However, the biological targets controlled by these ATPases are largely unknown. Using g...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1276305
更新日期:2005-04-15 00:00:00
abstract::GRF2, an abundant yeast protein of Mr approximately 127,000, binds to the GAL upstream activating sequence (UASG) and creates a nucleosome-free region of approximately 230 bp. Purified GRF2 binds to sequences found in many other UASs, in the 35S rRNA enhancer, at centromeres, and at telomeres. Although GRF2 stimulates...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.503
更新日期:1990-04-01 00:00:00
abstract::Orexin A and Orexin B (also known as hypocretins) are neuropeptides that bind two related G-coupled protein receptors (OXR1 and OXR2) and thus induce wakefulness, food consumption, and locomotion. Conversely, deletion of the orexin gene in mice produces a condition similar to canine and human narcolepsy. Despite the c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1584307
更新日期:2007-11-15 00:00:00
abstract::DNA replication remains unfinished in many Drosophila polyploid cells, which harbor disproportionately fewer copies of late-replicating chromosomal regions. By analyzing paired-end high-throughput sequence data from polytene larval salivary gland cells, we define 112 underreplicated (UR) euchromatic regions 60-480 kb ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.245811.114
更新日期:2014-08-15 00:00:00
abstract::The labial (lab) gene of Drosophila melanogaster is necessary for the proper development of the embryonic (larval) and adult head. We have identified the lab transcription unit within the proximal portion of the Antennapedia Complex (ANT-C) by mapping the molecular lesions associated with chromosomally rearranged lab ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.3.399
更新日期:1989-03-01 00:00:00
abstract::Constitutive activation of the Wnt/APC/beta-catenin pathway is a frequent initiating event in gastrointestinal carcinogenesis. Mutations in the Adenomatous Polyposis Coli (APC) gene up-regulate Wnt signaling by stabilizing beta-catenin and causing activation of targets important in proliferation control. Here we show ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1260605
更新日期:2005-02-01 00:00:00
abstract::The liver is a unique organ with a remarkably high potential to regenerate upon injuries. In severely damaged livers where hepatocyte proliferation is impaired, facultative liver progenitor cells (LPCs) proliferate and are assumed to contribute to regeneration. An expansion of LPCs is often observed in patients with v...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.204776.112
更新日期:2013-01-15 00:00:00
abstract::Experiments in Xenopus have illustrated the importance of extracellular morphogens for embryonic gene regulation in vertebrates. Much less is known about how induction leads to the correct positioning of boundaries; for example, between germ layers. Here we report that the neuroectoderm/mesoderm boundary is controlled...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.409507
更新日期:2007-04-15 00:00:00
abstract::Chromatin-modifying enzymes are known to be critical components for the correct differentiation of embryonic stem cells into specific lineages, such as neurons. Recently, the role of Polycomb group proteins has been studied in the specification and differentiation of muscle stem cells. In this perspective, we review a...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.2054311
更新日期:2011-05-15 00:00:00
abstract::Sox2 is expressed in basal epithelial cells of the tongue, with high levels in taste bud placodes, fungiform papillae, and mature taste cells, and low levels in filiform papillae. High Sox2 expression appears to lie downstream from canonical Wnt signaling. In hypomorphic Sox2(EGFP/LP) embryos, placodes form but no mat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1457106
更新日期:2006-10-01 00:00:00
abstract::The mammary tumor-associated proto-oncogene Wnt-1/int-1 encodes a secreted protein implicated in the regulation of neural development in vertebrates and segmental pattern in Drosophila. Using a PCR-based strategy, we isolated cDNAs encoding six novel, related proteins that are expressed in fetal mice. Predicted protei...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.12b.2319
更新日期:1990-12-01 00:00:00
abstract::C-factor, the product of the csgA gene, is a cell-surface associated short-range intercellular signaling protein in Myxococcus xanthus. C-factor is required for at least four responses during starvation-induced fruiting body morphogenesis: rippling, aggregation, sporulation, and full expression of the csgA gene, all o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.6.740
更新日期:1996-03-15 00:00:00
abstract::We have purified and cloned a new splicing factor, KSRP. KSRP is a component of a multiprotein complex that binds specifically to an intronic splicing enhancer element downstream of the neuron-specific c-src N1 exon. This 75-kD protein induces the assembly of five other proteins, including the heterogeneous nuclear ri...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.8.1023
更新日期:1997-04-15 00:00:00
abstract::RNase MRP is a ribonucleoprotein endoribonuclease that has been shown to cleave mitochondrial primer RNA sequences from a variety of sources. Most of the RNase MRP activity is found in the nucleus where it plays a role in the processing of 5.8S rRNA. A temperature-conditional point mutation in the yeast RNA component ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.21.2617
更新日期:1994-11-01 00:00:00
abstract::The ultraviolet (UV)-induced (6-4) pyrimidine-pyrimidone photoproduct [(6-4) PP] confers a large structural distortion in DNA. Here we examine in human cells the roles of translesion synthesis (TLS) DNA polymerases (Pols) in promoting replication through a (6-4) TT photoproduct carried on a duplex plasmid where bidire...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1872810
更新日期:2010-01-15 00:00:00
abstract::Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARgamma coactivator-1 (PGC-1) alpha and beta have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1alpha and PGC-1beta ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1661708
更新日期:2008-07-15 00:00:00
abstract::An RNA-based gene silencing pathway that protects bacteria and archaea from viruses and other genome invaders is hypothesized to arise from guide RNAs encoded by CRISPR loci and proteins encoded by the cas genes. CRISPR loci contain multiple short invader-derived sequences separated by short repeats. The presence of v...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1742908
更新日期:2008-12-15 00:00:00