Relative position and strengths of poly(A) sites as well as transcription termination are critical to membrane versus secreted mu-chain expression during B-cell development.

Galli, Gabriella; Guise, Jeffrey W.; McDevitt, Michael A.; Tucker, P W; Nevins, Joseph R.

doi:10.1101/gad.1.5.471

Cited by 106 publications

(84 citation statements)

References 26 publications

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“…In immature B cells and mature B cells, the membrane mRNA form is produced, and the secretory poly(A) site is inactive (Lamson and Koshland 1984). Upon differentiation, the secretory poly(A) site is activated and the secretory form of mRNA is expressed (Galli et al 1987(Galli et al , 1988Peterson et al 1991;Takagaki et al 1996). In addition, the secretory mRNA's stability is increased (Mason et al 1988;Cox and Emtage 1989).…”

Section: Introductionmentioning

confidence: 95%

Non-snRNP U1A levels decrease during mammalian B-cell differentiation and release the IgM secretory poly(A) site from repression

Gunderson²,

Phillips

2005

RNA

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A regulated shift from the production of membrane to secretory forms of Immunoglobulin M (IgM) mRNA occurs during B cell differentiation due to the activation of an upstream secretory poly(A) site. U1A plays a key role in inhibiting the expression of the secretory poly(A) site by inhibiting both cleavage at the poly(A) site and subsequent poly(A) tail addition. However, how the inhibitory effect of U1A is alleviated in differentiated cells, which express the secretory poly(A) site, is not known. Using B cell lines representing different stages of B cell differentiation, we show that the amount of U1A available to inhibit the secretory poly(A) site is reduced in differentiated cells. Undifferentiated B cells have more total U1A than differentiated cells and a greater proportion of this is not associated with the U1snRNP. We show that this is available to inhibit poly(A) addition at the secretory poly(A) site using cold competitor RNA oligos to de-repress poly(A) addition in nuclear extracts from the respective cell lines. In addition, endogenous non-snRNP associated U1A-immunopurified from the different cell lines-inhibits poly(A) polymerase activity proportional to U1A recovered, suggesting that available U1A level alone is responsible for changes in its inhibitory effect at the secretory IgM poly (A) site.

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Section: Introductionmentioning

confidence: 95%

Non-snRNP U1A levels decrease during mammalian B-cell differentiation and release the IgM secretory poly(A) site from repression

Gunderson²,

Phillips

2005

RNA

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“…By moving elements of the gene around, thus changing the length of the intron between μS and μM exons, the Nevins and Tucker groups (Galli et al 1987(Galli et al , 1988 concluded that the choice was not due to proteins in plasma cells (plasmacytoma cells) and mature B cells (lymphoma cells) that dictated splice choice because plasmids that contained only one of the two 3 ′ terminal exons and polyA sites were expressed equally. The DSX pre-mRNA transcript is processed differently in females and males.…”

Section: Immunoglobulin Chains: Mμm and Mμs Chainsmentioning

confidence: 99%

Reflections on the history of pre-mRNA processing and highlights of current knowledge: A unified picture

Darnell¹

2013

RNA

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Several strong conclusions emerge concerning pre-mRNA processing from both old and newer experiments. The RNAPII complex is involved with pre-mRNA processing through binding of processing proteins to the CTD (carboxyl terminal domain) of the largest RNAPII subunit. These interactions are necessary for efficient processing, but whether factor binding to the CTD and delivery to splicing sites is obligatory or facilitatory is unsettled. Capping, addition of an m 7 Gppp residue (cap) to the initial transcribed residue of a pre-mRNA, occurs within seconds. Splicing of pre-mRNA by spliceosomes at particular sites is most likely committed during transcription by the binding of initiating processing factors and ∼50% of the time is completed in mammalian cells before completion of the primary transcript. This fact has led to an outpouring in the literature about "cotranscriptional splicing." However splicing requires several minutes for completion and can take longer. The RNAPII complex moves through very long introns and also through regions dense with alternating exons and introns at an average rate of ∼3 kb per min and is, therefore, not likely detained at each splice site for more than a few seconds, if at all. Cleavage of the primary transcript at the 3 ′ end and polyadenylation occurs within 30 sec or less at recognized polyA sites, and the majority of newly polyadenylated pre-mRNA molecules are much larger than the average mRNA. Finally, it seems quite likely that the nascent RNA most often remains associated with the chromosomal locus being transcribed until processing is complete, possibly acquiring factors related to the transport of the new mRNA to the cytoplasm.

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“…Two types of experiments strongly suggested that the poly(A) site switch does not require any gene-speci¢c factor. In one experiment it was shown that the switch operated only when the two poly(A) sites competed in the same pre-mRNA but not when they were located in di¡erent transcription units [95,96]. In the second type, a gene was built that contained a similar arrangement of alternative splice and poly(A) sites as the IgM heavy chain gene, but was composed of di¡erent sequences.…”

Section: Regulatory Aspectsmentioning

confidence: 99%

3′-End processing of pre-mRNA in eukaryotes

Wahle¹

1999

FEMS Microbiology Reviews

180

236

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Abstract3P-Ends of almost all eukaryotic mRNAs are generated by endonucleolytic cleavage and addition of a poly(A) tail. In mammalian cells, the reaction depends on the sequence AAUAAA upstream of the cleavage site, a degenerate GU-rich sequence element downstream of the cleavage site and stimulatory sequences upstream of AAUAAA. Six factors have been identified that carry out the two reactions. With a single exception, they have been purified to homogeneity and cDNAs for 11 subunits have been cloned. Some of the cooperative RNA-protein and protein-protein interactions within the processing complex have been analyzed, but many details, including the identity of the endonuclease, remain unknown. Several examples of regulated polyadenylation are being analyzed at the molecular level. In the yeast Saccharomyces cerevisiae, sequences directing cleavage and polyadenylation are more degenerate than in metazoans, and a downstream element has not been identified. The list of processing factors may be complete now with approximately a dozen polypeptides, but their functions in the reaction are largely unknown. 3P-Processing is known to be coupled to transcription. This connection is thought to involve interactions of processing factors with the mRNA cap as well as with RNA polymerase II. ß

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Relative position and strengths of poly(A) sites as well as transcription termination are critical to membrane versus secreted mu-chain expression during B-cell development.

Cited by 106 publications

References 26 publications

Non-snRNP U1A levels decrease during mammalian B-cell differentiation and release the IgM secretory poly(A) site from repression

Non-snRNP U1A levels decrease during mammalian B-cell differentiation and release the IgM secretory poly(A) site from repression

Reflections on the history of pre-mRNA processing and highlights of current knowledge: A unified picture

3′-End processing of pre-mRNA in eukaryotes

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