The half-life of immunoglobulin mRNA increases during B-cell differentiation: a possible role for targeting to membrane-bound polysomes.

Mason, John O.; Williams, Gareth T.; Neuberger, Michael S.

doi:10.1101/gad.2.8.1003

Cited by 59 publications

(33 citation statements)

References 41 publications

(53 reference statements)

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“…However, the physiological factors that trigger the UPR in the course of PC differentiation are not at all well defined. Mature naive B cells synthesize equal amounts of m and s (39). In the course of PC differentiation, B cells shift from synthesis of the m to predominantly s (3).…”

Section: Discussionmentioning

confidence: 99%

AID−/−μs−/− Mice Are Agammaglobulinemic and Fail to Maintain B220−CD138+ Plasma Cells

Kumazaki

Tirosh

Maehr

et al. 2007

The Journal of Immunology

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The terminal stage of B cell differentiation culminates in the formation of plasma cells (PC), which secrete large quantities of Igs. Despite recent progress in understanding the molecular aspect of PC differentiation and maintenance, the requirement for the synthesis of secretory Igs as a contributing factor has not been explored. To address this issue, we generated activation-induced cytidine deaminase (AID)/secretory μ-chain (μs) double-knockout mice, in which a normally diverse repertoire of B cell receptors is retained, yet B cells are unable to synthesize secretory Igs. These mice possess polyclonal B cells but have no serum Igs. Following immunization in vivo, PCs, identified by CD138 expression and loss of the B220 marker, were starkly reduced in number in spleen and bone marrow of AID−/−μs−/− agammaglobulinemic mice compared with wild-type mice. Upon mitogenic stimulation in vitro, AID−/−μs−/− B cells differentiated into plasmablasts to some extent, but showed reduced survival compared with wild-type B cells. We found no evidence that this reduced survival was attributable to accumulation of membrane IgM. Our results indicate that the synthesis of secretory Igs is a requirement for maintenance of B220−CD138+ PCs.

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Section: Discussionmentioning

confidence: 99%

AID−/−μs−/− Mice Are Agammaglobulinemic and Fail to Maintain B220−CD138+ Plasma Cells

Kumazaki

Tirosh

Maehr

et al. 2007

The Journal of Immunology

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“…These are J558L, M12.4.1, and WEHI 231, which we used previously (Phillips et al 2001). J558Ls are a plasmacytoma cell line that has lost endogenous IgM heavy chain (m) and produce only the secretory form of m chain mRNA from a transfected gene construct (Oi et al 1983;Mason et al 1988), M12.4.1 cells produce IgG2a and aproximately twofold secretory versus membrane m-mRNA from a transfected m chain construct (Kim et al 1979) and WEHI 231 is an immature B cell line that produces more endogenous membrane than secretory m mRNA (Mason et al 1988). …”

Section: Resultsmentioning

confidence: 99%

“…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). U1A protein has been shown to inhibit activation of the secretory poly(A) site both on the level of cleavage and of poly(A) addition, the latter resulting in destabilization (Phillips et al 2001(Phillips et al , 2004.…”

Section: Introductionmentioning

confidence: 99%

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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“…Transcript localization could be a mechanism for targeting specific mRNAs for degradation (20,37). However, BBT mRNA, which lacks localization sequences but contains the BIE, is unstable.…”

Section: Discussionmentioning

confidence: 99%

Developmental Regulation of bicoid mRNA Stability Is Mediated by the First 43 Nucleotides of the 3′ Untranslated Region

Surdej

Jacobs-Lorena

1998

Molecular and Cellular Biology

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During the transition from the maternal to the zygotic developmental program, the expression of genes important for pattern formation or cell cycle regulation changes dramatically. Rapid changes in gene expression are achieved in part through the control of mRNA stability. This report focuses on bicoid, a gene essential for formation of anterior embryonic structures in Drosophila melanogaster. bicoid mRNA is synthesized exclusively during oogenesis. Here, we show that bicoid mRNA stability is regulated. While bicoid mRNA is stable in retained oocytes, in unfertilized eggs, and during the first 2 h of embryogenesis, specific degradation is activated at cellularization of the blastoderm. To identify cis-acting sequences required for bicoid mRNA's regulated stability, fusions between bicoid and genes producing stable mRNAs were introduced into the Drosophila germ line by P-element-mediated transformation. The analysis of the fusion mRNAs identified a bicoid instability element (BIE) contained within a 43-nucleotide sequence immediately following the stop codon. The BIE is sufficient to destabilize the otherwise-stable ribosomal protein A1 mRNA and is separable from the previously identified bicoid mRNA localization signals and from the "nanos response element." Similar mechanisms may regulate a class of developmentally important maternal genes whose mRNA has a temporal profile similar to that of bicoid.

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The half-life of immunoglobulin mRNA increases during B-cell differentiation: a possible role for targeting to membrane-bound polysomes.

Cited by 59 publications

References 41 publications

AID−/−μs−/− Mice Are Agammaglobulinemic and Fail to Maintain B220−CD138+ Plasma Cells

AID−/−μs−/− Mice Are Agammaglobulinemic and Fail to Maintain B220−CD138+ Plasma Cells

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

Developmental Regulation of bicoid mRNA Stability Is Mediated by the First 43 Nucleotides of the 3′ Untranslated Region

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