RNA Splicing in the Transition from B Cells to Antibody-Secreting Cells: The Influences of ELL2, Small Nuclear RNA, and Endoplasmic Reticulum Stress.
RNA Splicing in the Transition from B Cells to Antibody-Secreting Cells: The Influences of ELL2, Small Nuclear RNA, and Endoplasmic Reticulum Stress.
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DOI：
10.4049/jimmunol.1800557
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发表时间：
2018-11-15
期刊：
影响因子：
--
通讯作者：
Milcarek C
中科院分区：
文献类型：
--
作者：
Nelson AM;Carew NT;Smith SM;Milcarek C
In the transition from B cells to antibody secreting cells (ASCs) many genes are induced, like ELL2, Irf4, Prdm1, Xbp1, while other mRNAs do not change in abundance. Nonetheless using splicing array technology and mouse splenic B cells +/− LPS we found that induced and “un-induced” genes can show large differences in splicing patterns between the cell stages which could influence ASC development. We found that about 55% of these splicing changes depend on ELL2, a transcription elongation factor that influences expression levels and splicing patterns of ASC signature genes, genes in the cell-cycle and N-glycan biosynthesis and processing pathways, and the secretory vs membrane forms of the Ig heavy chain mRNA. Some of these changes occur when ELL2 binds directly to the genes encoding those mRNAs while some of the changes are indirect. To attempt to account for the changes that occur in RNA splicing before or without ELL2 induction, we examined the amount of the snRNA molecules (small nuclear RNA) and found that they were significantly decreased within 18 hours of LPS stimulation and stayed low until 72 hours. Correlating with this, at 18 hours after LPS, endo-reticular (ER) stress and Ire1 phosphorylation are induced. Inhibiting the regulated Ire1 dependent mRNA decay pathway (RIDD) with 4u8C correlates with the reduction in snRNA and changes in the normal splicing patterns at 18 hours. Thus we conclude that the RNA splicing patterns in ASCs are shaped early by ER stress and Ire1 phosphorylation and later by ELL2 induction.
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影响因子：
4.8
作者：
Milcarek, Christine;Albring, Michael;Park, Kyung Soo
通讯作者：
Park, Kyung Soo
DOI：
10.4049/jimmunol.1401608
发表时间：
2014-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Park KS;Bayles I;Szlachta-McGinn A;Paul J;Boiko J;Santos P;Liu J;Wang Z;Borghesi L;Milcarek C
通讯作者：
Milcarek C
影响因子：
64.5
作者：
Cheng Z;Otto GM;Powers EN;Keskin A;Mertins P;Carr SA;Jovanovic M;Brar GA
通讯作者：
Brar GA
DOI：
10.1073/pnas.95.19.11095
发表时间：
1998-09-15
影响因子：
11.1
作者：
Martincic, K;Campbell, R;Milcarek, C
通讯作者：
Milcarek, C
影响因子：
10.5
作者：
Henry, RW;Mittal, V;Hernandez, N
通讯作者：
Hernandez, N