The cDNA sequences of the sea urchin U7 small nuclear RNA suggest specific contacts between histone mRNA precursor and U7 RNA during RNA processing.

Strub, Katharina; Galli, Gabriella; Busslinger, Meinrad; Birnstiel, Max L.

doi:10.1002/j.1460-2075.1984.tb02212.x

Cited by 165 publications

(128 citation statements)

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“…Thus, the existence of a histone mRNA 3' processing activity in Xenopus laevis oocytes and Drosophila melanogaster tissue culture cell extracts has been clearly demonstrated (4,25,43). Furthermore, it has been shown that this activity is associated with a small nuclear RNA U7 (12,52) in a similar way to the involvement of the small nuclear RNA Ul in intronic splicing (24,27,42,47). These results indicate that transcriptional termination is likely to occur separately from 3'-end processing in histone genes.…”

mentioning

confidence: 79%

Tripartite sequences within and 3' to the sea urchin H2A histone gene display properties associated with a transcriptional termination process.

Johnson¹,

Norman²,

Reeve³

et al. 1986

Mol. Cell. Biol.

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We have defined a DNA sequence that behaves as an RNA polymerase II termination signal by using the human HeLa cell transient expression system. Surprisingly, this sequence is tripartite, including part of the coding region of the sea urchin H2A histone gene together with two separate sequences in the 3' flanking region of the gene. We demonstrate that this signal functions both in its normal gene environment and also when placed within the human a-globin gene. However, we have failed to detect a discrete 3' terminus. Rather, our data indicate the, presence of an extremely heterogeneous series of nonpolyadenylated RNAs. These heterogeneous nonpolyadenylated RNAs are stable when transcribed from the intact histone gene but are highly unstable within the human a-globin gene. This provides evidence for the role of poly(A) in the stability of mnRNA.Initiation of transcription in eucaryotic RNA polymerase II (polII) genes is a highly regulated and in some instances well-defined process (see reference 28 for a review). In contrast, termination of transcription in polII genes is ill defined and may not be a regulated process. The principal cause of this uncertainty is the rapid posttranscriptional processing of primary RNA transcripts to mature mRNA (see reference 40 for a review). The fact that introns are spliced out of the polII gene transcript is well documented. Similarly, the generation of mRNA 3' termini for both polyadenylated [poly(A)+] mRNA and nonpolyadenylated [poly(A)-] histone mRNA by a processing event has been recently established (see references 5 and 44 for reviews).The best evidence for processing of mRNA 3' ends comes from studies on histone mRNA. Thus, the existence of a histone mRNA 3' processing activity in Xenopus laevis oocytes and Drosophila melanogaster tissue culture cell extracts has been clearly demonstrated (4,25,43). Furthermore, it has been shown that this activity is associated with a small nuclear RNA U7 (12, 52) in a similar way to the involvement of the small nuclear RNA Ul in intronic splicing (24,27,42,47). These results indicate that transcriptional termination is likely to occur separately from 3'-end processing in histone genes. Evidence of a similar nature in poly(A)+ mRNA genes is now becoming available. Moore and Sharp (37) have recently shown that synthetic RNAs extending beyond an adenovirus poly(A) site can be efficiently and accurately cleaved and polyadenylated by using in vitro cell extracts.Further evidence for transcriptional termination separate from nmRNA 3'-end formation comes from hybridization analysis of pulse-labeled RNA transcripts. Using these techniques, Nevins and Darnell (38) and Fraser et al. (11) deduced that the major late gene transcripts of adenovirus extend beyond the various late mRNA poly(A) sites to near the end of the viral genome. Similarly, transcription extends beyond the adenovirus early region 2 and 4 poly(A) sites and the simian virus 40 (SV40) late poly(A) site (10, 39). These viral transcription experiments were performed on pulse-* Corr...

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mentioning

confidence: 79%

Tripartite sequences within and 3' to the sea urchin H2A histone gene display properties associated with a transcriptional termination process.

Johnson¹,

Norman²,

Reeve³

et al. 1986

Mol. Cell. Biol.

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“…The discovery of the U7 RNA as an essential component of the processing machinery derives from one such experimental design. cDNA cloning and sequencing of the RNA led to the hypothesis of a base-paired intermediate during 3' processing of the histone mRNA in which the 5' portion of the sea urchin U7 RNA basepairs with both the GAAAGA of the downstream conserved CAAGAAAGA moitif of the H3 mRNA and with portions of the stem-loop structure (Strub et al, 1984;Strub and Bimstiel, 1986) leaving the precursor sequences intervening between these conserved motifs in an unpaired loop. The terminal palindrome and downstream consensus spacer sequences occur only in histone genes which are regulated in the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Generation of histone mRNA 3′ ends by endonucleolytic cleavage of the pre-mRNA in a snRNP-dependent in vitro reaction.

Gick¹,

Krämer²,

Keller³

et al. 1986

The EMBO Journal

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Incubation of SP6 generated mouse histone H4 mRNA precursors in nuclear extracts of HeLa cells yields processed mRNA species which end on the 3' adenosine of the conserved terminal ACCA sequence not unlike ten different histone mRNAs isolated from sea urchin embryos which end either on the 3' C or A. In the presence of 20 mM EDTA, the cleaved off 3' spacer portions of the RNA transcripts are readily detected, hence the 3' ends of histone mRNAs arise as a consequence of endonucleolytic cleavage(s) of the precursor RNA. The in vitro cleavage reaction is specifically inhibited by human antisera of the Sm-serotype, but not by control sera and can be rescued by the addition of a preparation of partially purified small nuclear RNPs to the antibody-depleted extract. Interestingly, the snRNP preparation is sufficient to elicit 3' processing of pre-mRNA in the absence of added nuclear extract.

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“…Later studies using the same in vivo system proved that histone mRNAs are in fact formed from longer precursors by a post-transcriptional endonucleolytic cleavage at the 3' end (Birchmeier et al, 1984;Krieg and Melton, 1984). These studies resulted in the identification of a 60-nucleotide RNA designated U7 snRNA as an essential component of this 3' end processing reaction (Galli et al, 1983;Strub et al, 1984). Important insights into the mechanism of 3' end processing of histone pre-mRNAs have been subsequently provided using in vitro systems based on nuclear extracts from mammalian cells capable of accurate and efficient cleavage of pre-synthesized histone pre-mRNAs Furger et al, 1998;Gick et al, 1986;Mowry and Steitz, 1987a).…”

Section: Sequence Elements In 3' End Processing Of Histone Pre-mrnasmentioning

confidence: 99%

Formation of the 3′ end of histone mRNA: Getting closer to the end

Domiński

Marzluff

2007

Gene

159

180

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Nearly all eukaryotic mRNAs end with a poly (A) tail that is added to their 3' end by the ubiquitous cleavage/polyadenylation machinery. The only known exception to this rule are metazoan replication dependent histone mRNAs, which end with a highly conserved stem-loop structure. This distinct 3' end is generated by specialized 3'end processing machinery that cleaves histone pre-mRNAs 4-5 nucleotides downstream of the stem-loop and consists of the U7 small nuclear RNP (snRNP) and number of protein factors. Recently, the U7 snRNP has been shown to contain a unique Sm core that differs from that of the spliceosomal snRNPs, and an essential heat labile processing factor has been identified as symplekin. In addition, cross-linking studies have pinpointed CPSF-73 as the endonuclease, which catalyzes the cleavage reaction. Thus, many of the critical components of the 3' end processing machinery are now identified. Strikingly, this machinery is not as unique as initially thought but contains a number of factors involved in cleavage/polyadenylation, suggesting that the two mechanisms have a common evolutionary origin. The greatest challenge that lies ahead is to determine how all these factors interact with each other to form a catalytically competent processing complex capable of cleaving histone pre-mRNAs.

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The cDNA sequences of the sea urchin U7 small nuclear RNA suggest specific contacts between histone mRNA precursor and U7 RNA during RNA processing.

Cited by 165 publications

References 47 publications

Tripartite sequences within and 3' to the sea urchin H2A histone gene display properties associated with a transcriptional termination process.

Tripartite sequences within and 3' to the sea urchin H2A histone gene display properties associated with a transcriptional termination process.

Generation of histone mRNA 3′ ends by endonucleolytic cleavage of the pre-mRNA in a snRNP-dependent in vitro reaction.

Formation of the 3′ end of histone mRNA: Getting closer to the end

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