Abstract:
:Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons that circularize in Drosophila, but the underlying mechanisms by which these circular RNAs are generated are largely unknown. Here, using extensive mutagenesis of expression plasmids and RNAi screening, we reveal that circularization of the Drosophila laccase2 gene is regulated by both intronic repeats and trans-acting splicing factors. Analogous to what has been observed in humans and mice, base-pairing between highly complementary transposable elements facilitates backsplicing. Long flanking repeats (∼ 400 nucleotides [nt]) promote circularization cotranscriptionally, whereas pre-mRNAs containing minimal repeats (<40 nt) generate circular RNAs predominately after 3' end processing. Unlike the previously characterized Muscleblind (Mbl) circular RNA, which requires the Mbl protein for its biogenesis, we found that Laccase2 circular RNA levels are not controlled by Mbl or the Laccase2 gene product but rather by multiple hnRNP (heterogeneous nuclear ribonucleoprotein) and SR (serine-arginine) proteins acting in a combinatorial manner. hnRNP and SR proteins also regulate the expression of other Drosophila circular RNAs, including Plexin A (PlexA), suggesting a common strategy for regulating backsplicing. Furthermore, the laccase2 flanking introns support efficient circularization of diverse exons in Drosophila and human cells, providing a new tool for exploring the functional consequences of circular RNA expression across eukaryotes.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Kramer MC,Liang D,Tatomer DC,Gold B,March ZM,Cherry S,Wilusz JEdoi
10.1101/gad.270421.115subject
Has Abstractpub_date
2015-10-15 00:00:00pages
2168-82issue
20eissn
0890-9369issn
1549-5477pii
gad.270421.115journal_volume
29pub_type
杂志文章abstract::Interactions required for inhibition of poly(A) polymerase (PAP) by the U1 snRNP-specific U1A protein, a reaction whose function is to autoregulate U1A protein production, are examined. PAP inhibition requires a substrate RNA to which at least two molecules of U1A protein can bind tightly, but we demonstrate that the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.6.761
更新日期:1997-03-15 00:00:00
abstract::The ECS (Elongin B/C-Cul2/Cul5-SOCS-box protein) complex is a member of a family of ubiquitin ligases that share a Cullin-Rbx module. SOCS-box proteins recruit substrates to the ECS complex and are linked to Cullin-Rbx via Elongin B/C. VHL has been implicated as a SOCS-box protein, but lacks a C-terminal sequence (dow...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1252404
更新日期:2004-12-15 00:00:00
abstract::The transcription factor TFIIB plays a central role in preinitiation complex assembly, providing a bridge between promoter-bound TFIID and RNA Polymerase II. TFIIB possesses sequence-specific DNA-binding ability and interacts with the TFIIB-recognition element (BRE), present in many promoters. Here we show that the BR...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.206901
更新日期:2001-11-15 00:00:00
abstract::Our understanding of eukaryotic transcriptional activation mechanisms has been hampered by an inability to identify the direct in vivo targets of activator proteins, primarily because of lack of appropriate experimental methods. To circumvent this problem, we have developed a fluorescence resonance energy transfer (FR...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1148404
更新日期:2004-02-01 00:00:00
abstract::In meiosis I, homologous chromosomes pair and then attach to the spindle so that the homologs can be pulled apart at anaphase I. The segregation of homologs before pairing would be catastrophic. We describe two mechanisms that prevent this. First, in early meiosis, Ipl1, the budding yeast homolog of the mammalian Auro...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.227454.113
更新日期:2013-10-01 00:00:00
abstract::Pcf11 is one of numerous proteins involved in pre-mRNA 3'-end processing and transcription termination. Using elongation complexes (ECs) formed from purified yeast RNA polymerase II (Pol II), we show that a 140-amino acid polypeptide from yeast Pcf11 is capable of dismantling the EC in vitro. This action depends on th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1296305
更新日期:2005-07-01 00:00:00
abstract::The POU transcription factor Oct-4 is expressed specifically in the germ line, pluripotent cells of the pregastrulation embryo and stem cell lines derived from the early embryo. Osteopontin (OPN) is a protein secreted by cells of the preimplantation embryo and contains a GRGDS motif that can bind to specific integrin ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.13.2073
更新日期:1998-07-01 00:00:00
abstract::Many small nucleolar RNAs (snoRNAs) in vertebrates are encoded within introns of protein genes. We have reported previously that two isoforms of human U17 snoRNA are encoded in introns of the cell-cycle regulatory gene, RCC1. We have now investigated the mechanism of processing of U17 RNAs and of another intron-encode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.11.1411
更新日期:1995-06-01 00:00:00
abstract::The integration of viral DNA into the host genome is an essential step in the retrovirus life cycle. To understand this process better, we have examined the native state of viral DNA in cells acutely infected by murine leukemia virus (MLV), using both a physical assay for viral DNA and a functional assay for integrati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.4.469
更新日期:1989-04-01 00:00:00
abstract::The td, nrdB, and sunY introns of bacteriophage T4 each contain a long open reading frame (ORF). These ORFs are preceded by functional T4 late promoters and, in the case of the nrdB intron ORF, a functional middle promoter. Expression of phage-encoded intron ORF-lacZ fusions indicates that these T4 genes are highly re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.12b.1791
更新日期:1988-12-01 00:00:00
abstract::The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.257675.114
更新日期:2015-04-15 00:00:00
abstract::The human Y-family DNA polymerases, Poliota, Poleta, and Polkappa, function in promoting replication through DNA lesions. However, because of their low fidelity, any involvement of these polymerases in DNA synthesis during base excision repair (BER) would be highly mutagenic. Mechanisms, therefore, must exist to exclu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1146103
更新日期:2003-11-15 00:00:00
abstract::Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1823109
更新日期:2009-08-15 00:00:00
abstract::Morphogen gradients of secreted molecules play critical roles in the establishment of the spatial pattern of gene expression. During midgut development in Drosophila, secreted molecules of Decapentaplegic (Dpp) and Wingless (Wg) establish unique transcriptional regulation within target cells to specify the resultant c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.17.2724
更新日期:1998-09-01 00:00:00
abstract::Transcription of frog rDNA by mouse cell factors is the only documented exception to the observed species selectivity of rRNA gene expression. This heterologous transcription is authentic in that it uses the normal frog upstream and core promoter domains, as well as the normal mouse polymerase I transcription factors,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.1.52
更新日期:1990-01-01 00:00:00
abstract::The physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic β cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions impro...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.342378.120
更新日期:2021-01-14 00:00:00
abstract::The ability to initiate organs throughout the lifecycle is a unique feature of plant development that is executed by groups of stem cells called meristems. The balance between stem cell proliferation and organ initiation is carefully regulated and ensures that organs can be initiated in regular geometric patterns. To ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.208501
更新日期:2001-10-15 00:00:00
abstract::Histone deacetylase 3 (HDAC3) is one of four members of the human class I HDACs that regulates gene expression by deacetylation of histones and nonhistone proteins. Early studies have suggested that HDAC3 activity is regulated by association with the corepressors N-CoR and SMRT. Here we demonstrate that, in addition t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1286005
更新日期:2005-04-01 00:00:00
abstract::Treatment with retinoic acid (RA) is known to produce complex teratogenic effects in vertebrates, and its presence in the developing embryo as an endogenous substance has led to the suggestion that RA might be a natural morphogenetic agent. Although our understanding of the molecular mechanism of RA action has improve...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.8.1333
更新日期:1991-08-01 00:00:00
abstract::Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell-specific deletion of Max has a modest effect on B-cell development but completely abrogates Eµ-Myc-driven lymphomagenesis. While Max loss affects only a few hund...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.325878.119
更新日期:2019-09-01 00:00:00
abstract::Hepatocyte nuclear factor 1 (HNF-1) is a transcriptional regulatory protein possibly involved in the activation of many liver-specifically expressed genes. HNF-1 mRNA is restricted to a small number of tissues, suggesting that the HNF-1 gene itself is regulated at the transcriptional level. We have isolated and charac...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.12a.2225
更新日期:1991-12-01 00:00:00
abstract::The regulation of gene transcription is critical for the proper development and growth of an organism. The transcription of protein-coding genes initiates at the RNA polymerase II core promoter, which is a diverse module that can be controlled by many different elements such as the TATA box and downstream core promote...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1698108
更新日期:2008-10-15 00:00:00
abstract::The chromo domain was identified as a homologous protein motif between Polycomb (Pc)--a member of the Pc-group genes encoding transcriptional repressors of the homeotic genes--and HP1--a heterochromatin-associated protein encoded by the suppressor of position effect variegation gene Su(var)205. Together with previous ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.7.1241
更新日期:1992-07-01 00:00:00
abstract::Establishment of the steroid-producing Leydig cell lineage is an event downstream of Sry that is critical for masculinization of mammalian embryos. Neither the origin of fetal Leydig cell precursors nor the signaling pathway that specifies the Leydig cell lineage is known. Based on the sex-specific expression patterns...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.981202
更新日期:2002-06-01 00:00:00
abstract::One of the most common microsatellites in eukaryotes consists of tandem arrays of the dinucleotide GT. Although the study of the instability of such repetitive DNA has been extremely fruitful over the last decade, no biological function has been demonstrated for these sequences. We investigated the genetic behavior of...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-05-15 00:00:00
abstract::Over a period of many months, Xenopus oocytes stockpile large quantities of tRNA for use during the first few hours of embryogenesis. To test the idea that these tRNAs are transcribed from one set of genes and that another set is used by somatic cells, we used synthetic oligonucleotides to analyze the sequence and ste...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.8.1190
更新日期:1989-08-01 00:00:00
abstract::The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1664408
更新日期:2008-07-15 00:00:00
abstract::The connection between RNA and protein export from the nucleus was examined in the budding yeast Saccharomyces cerevisiae. NPL3 encodes an RNA-binding protein that shuttles in and out of the nucleus. Export of poly(A)+ RNA has been shown previously to be blocked in np13-1 mutants. To understand the role of Np13p in RN...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.10.1233
更新日期:1996-05-15 00:00:00
abstract::The spectrum of tumors associated with oncogenic Ras in humans often differs from those in mice either treated with carcinogens or engineered to sporadically express oncogenic Ras, suggesting that the mechanism of Ras transformation may be different in humans. Ras stimulates primarily three main classes of effector pr...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.993902
更新日期:2002-08-15 00:00:00
abstract::Dosage compensation in Drosophila occurs by a twofold increase in transcription per copy of X-linked genes in males (XY) compared with females (XX). msl-1 is one of four genes that are essential for dosage compensation in males, and MSL-1 protein is associated specifically with the male X chromosome. To explore the ba...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.6.698
更新日期:1994-03-15 00:00:00