Binding of the Drosophila transformer and transformer-2 proteins to the regulatory elements of doublesex primary transcript for sex-specific RNA processing.

Inoue, Kimiko; Hoshijima, Kazuyuki; Higuchi, Ikuko; Sakamoto, Hiroshi; Shimura, Yoichi

doi:10.1073/pnas.89.17.8092

Cited by 151 publications

(147 citation statements)

References 27 publications

Supporting

Mentioning

140

Contrasting

Order By: Relevance

“…The sequence motif involved in nonsense-mediated mRNA decay is another example of a short RNA repeat involved in posttranscriptional regulation. Short RNA sequences that modulate both mRNA turnover and splicing have been identified (10,27,33,34,36,37,63,68,73,74,77). As with the results presented here, sequences flanking these motifs can influence their activity.…”

Section: Discussionmentioning

confidence: 66%

Identification and Characterization of a Sequence Motif Involved in Nonsense-Mediated mRNA Decay

Zhang

Ruiz-Echevarría²,

Quan

et al. 1995

Molecular and Cellular Biology

123

View full text Add to dashboard Cite

In both prokaryotes and eukaryotes, nonsense mutations in a gene can enhance the decay rate or reduce the abundance of the mRNA transcribed from that gene, and we call this process nonsense-mediated mRNA decay. We have been investigating the cis-acting sequences involved in this decay pathway. Previous experiments have demonstrated that, in addition to a nonsense codon, specific sequences 3 of a nonsense mutation, which have been defined as downstream elements, are required for mRNA destabilization. The results presented here identify a sequence motif (TGYYGATGYYYYY, where Y stands for either T or C) that can predict regions in genes that, when positioned 3 of a nonsense codon, promote rapid decay of its mRNA. Sequences harboring two copies of the motif from five regions in the PGK1, ADE3, and HIS4 genes were able to function as downstream elements. In addition, four copies of this motif can function as an independent downstream element. The sequences flanking the motif played a more significant role in modulating its activity when fewer copies of the sequence motif were present. Our results indicate the sequences 5 of the motif can modulate its activity by maintaining a certain distance between the sequence motif and the termination codon. We also suggest that the sequences 3 of the motif modulate the activity of the downstream element by forming RNA secondary structures. Consistent with this view, a stem-loop structure positioned 3 of the sequence motif can enhance the activity of the downstream element. This sequence motif is one of the few elements that have been identified that can predict regions in genes that can be involved in mRNA turnover. The role of these sequences in mRNA decay is discussed.The rates at which mRNAs decay play an important role in regulating gene expression. mRNA half-lives can vary from each other by as much as 100-fold (28,55,59,62,64), and this variation determines, in part, the cytoplasmic abundance of these RNAs. In addition, the decay rate of an mRNA can be modulated, and its half-life can vary depending on the cell type or the environmental situation of the cell (e.g., hormones, stress, cell cycle, etc. [3,55,62]). The goal of our work is to understand the cellular mechanisms that determine the stability of mRNAs.We are studying mRNA decay in the yeast Saccharomyces cerevisiae. Our results, as well as work from other laboratories, strongly indicate that the processes of mRNA turnover and translation are intimately linked and that understanding of this relationship is critical in elucidating the mechanism of mRNA decay (2, 5, 9, 11, 15, 21, 23, 29-31, 41, 53, 55-59, 76). The role of translation in determination of mRNA decay rates is direct, and, for certain instability elements identified in protein coding regions and 3Ј untranslated regions (3Ј-UTRs), translation of the protein coding region must occur in order for them to function (2,11,15,21,23,29,41,53,60,66,76).One clear example of the relationship between translation and mRNA decay is the observation that nonsense mutati...

show abstract

Section: Discussionmentioning

confidence: 66%

Identification and Characterization of a Sequence Motif Involved in Nonsense-Mediated mRNA Decay

Zhang

Ruiz-Echevarría²,

Quan

et al. 1995

Molecular and Cellular Biology

123

View full text Add to dashboard Cite

show abstract

“…resulting in alternative splicing (35)(36)(37). Thus, a few mutations in the splicing motif may change the alternative splicing pattern, thereby dramatically altering the phenotype.…”

Section: Species In the Explosively Speciated Lineage Have Acquired Cmentioning

confidence: 99%

The complexity of alternative splicing of hagoromo mRNAs is increased in an explosively speciated lineage in East African cichlids

Terai

Morikawa

Kawakami

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The adaptive radiation of cichlid fishes in the lakes of East Africa is a prime example of speciation. The choice of cichlid mates on the basis of a variety of coloration represents a potential basis for speciation that led to adaptive radiation. Here, we characterize the cichlid homolog of the zebrafish hagoromo (hag) gene that was recently cloned and characterized from a pigmentation mutant. Although only one hag mRNA was reported in zebrafish, cichlids express nine different hag mRNAs resulting from alternative splicing. The hag mRNAs are expressed between the myotome and the epidermis where pigment cells are located, suggesting the cichlid hag gene is involved in pigmentation. The hag mRNA splicing pattern does not fluctuate among individuals from each of two species, suggesting that alternative splice site choice is fixed within species. Furthermore, cichlids in lineages that underwent explosive speciation expressed a greater variety of hag mRNAs than those in lineages that did not undergo such a degree of speciation, suggesting that species in the explosively speciated lineage acquired a complex regulatory mechanism of alternative splicing over a very short evolutionary period. Here, we provide an example in which alternative splicing may play a role in mate choice, leading to cichlid speciation through diversification of gene function by production of multiple mRNAs from a single gene.

show abstract

“…1A). The dsx pre-mRNA requires an exonic splicing enhancer (ESE) in exon 4 for efficient processing in vitro and in vivo (31,(33)(34)(35)(36). To determine whether activators might affect ESE-dependent or ESE-independent processing differently, we compared splicing and 3Ј-end cleavage levels of Gal5HIV2dsx(ϩintron) transcripts, with or without a typical mammalian ESE consisting of six GAA repeats inserted into exon 4.…”

Section: Transcriptional Activators Influence Splicing and 3ј-endmentioning

confidence: 99%

Transcriptional Activators Control Splicing and 3′-End Cleavage Levels

Rosonina

Bakowski

McCracken

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

We have investigated whether transcriptional activators influence the efficiency of constitutive splicing and 3 -end formation, in addition to transcription levels. Remarkably, strong activators result in higher levels of splicing and 3 -cleavage than weak activators and can control the efficiency of these steps in pre-mRNA processing separately. The pre-mRNA processing stimulatory property of activators is dependent on their binding to promoters, but is not an indirect consequence of the levels of transcripts produced. Moreover, stimulation of splicing and cleavage by a strong activator operates by a mechanism that requires the carboxyl-terminal domain of RNA polymerase II. The splicing stimulatory property of activators was observed for unrelated transcripts and for separate introns within a transcript, indicating a possible general role for strong activators in facilitating pre-mRNA processing levels. The results suggest that the efficiency of constitutive splicing and 3 -end cleavage is closely coordinated with transcription levels by promoter-bound activators.The generation of mature mRNA involves the addition of an m 7 G cap at the 5Ј-end, splicing, and cleavage and polyadenylation at the 3Ј-end of precursor (pre-)mRNAs. Although these steps can occur in isolation of each other, the majority of pre-mRNA processing occurs as RNA polymerase II (pol II) 1 is transcribing. This is evident from numerous microscopy studies, in which the removal of most introns is observed to coincide with nascent transcript synthesis, as well as from more recent studies that demonstrate that transcription and pre-mRNA processing steps are physically coupled and can influence one another (1-3).The largest subunit of pol II contains a carboxyl-terminal domain (CTD), which in mammals consists of 52 repeats of the heptapeptide consensus sequence YSPTSPS (4, 5). Pol II at the stage of transcription initiation is associated with a large holoenzyme complex, which is recruited to promoters by sequence-specific transcriptional activators (6 -10). In some cases, stimulation of transcription by activators requires the CTD (11-13). Recent work has demonstrated that the CTD is also important for pre-mRNA processing. Truncation of the CTD in vivo reduces the efficiency of capping, splicing, and 3Ј-end formation (14 -16). Moreover, purified pol II, or the CTD itself, can stimulate splicing as well as the 3Ј-end processing of transcripts in vitro (17)(18)(19). Consistent with these results, factors involved in capping, splicing, and 3Ј-end formation have been found to interact with the CTD (1, 3, 20).It is not known at which stage of transcription different pre-mRNA processing components are recruited to transcription complexes, nor how CTD-associated components influence pre-mRNA processing. The 3Ј-end cleavage polyadenylation stimulatory factor (CPSF) interacts with the general transcription factor TFIID during transcription initiation (21), as well as with the CTD (15), indicating that it is recruited to transcription initiation complexes pr...

show abstract

Binding of the Drosophila transformer and transformer-2 proteins to the regulatory elements of doublesex primary transcript for sex-specific RNA processing.

Cited by 151 publications

References 27 publications

Identification and Characterization of a Sequence Motif Involved in Nonsense-Mediated mRNA Decay

Identification and Characterization of a Sequence Motif Involved in Nonsense-Mediated mRNA Decay

The complexity of alternative splicing of hagoromo mRNAs is increased in an explosively speciated lineage in East African cichlids

Transcriptional Activators Control Splicing and 3′-End Cleavage Levels

Contact Info

Product

Resources

About