Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells
10.1073/pnas.1214414109
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

B cells and plasma cells possess distinct RNA processing environments that respectively promote the expression of membrane-associated Ig by B cells versus the secretion of Ig by plasma cells. Through a combination of transcriptional profiling and screening using a lentiviral short-hairpin RNA interference library, we show that both the splicing factor hnRNPLL and the transcription elongation factor ELL2 modulate the ratio of secreted versus membrane-encodingIghg2btranscripts in MPC11 plasmacytoma cell lines. hnRNPLL and ELL2 are both highly expressed in primary plasma cells relative to B cells, but hnRNPLL bindsIghg2bmRNA transcripts and promotes an increase in levels of the membrane-encodingIghg2bisoform at the expense of the secretedIghg2bisoform, whereas ELL2 counteracts this effect and drives Ig secretion by increasing the frequency of the secretedIghg2bisoform. As in T cells, hnRNPLL also alters the splicing pattern of mRNA encoding the adhesion receptor CD44, promoting exon inclusion, and decreasing the overall level of CD44 expression. Further characterization of ELL2-dependent transcription by RNA-Seq revealed that ∼12% of transcripts expressed by plasma cells were differentially processed because of the activities of ELL2, including B-cell maturation antigen BCMA, a receptor with a defined role in plasma cell survival. Taken together, our data identify hnRNPLL and ELL2 as regulators of pre-mRNA processing in plasma cells.

Bibliography

Benson, M. J., Äijö, T., Chang, X., Gagnon, J., Pape, U. J., Anantharaman, V., Aravind, L., Pursiheimo, J.-P., Oberdoerffer, S., Liu, X. S., Lahesmaa, R., Lähdesmäki, H., & Rao, A. (2012). Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells. Proceedings of the National Academy of Sciences, 109(40), 16252–16257.

Authors 13
  1. Micah J. Benson (first)
  2. Tarmo Äijö (additional)
  3. Xing Chang (additional)
  4. John Gagnon (additional)
  5. Utz J. Pape (additional)
  6. Vivek Anantharaman (additional)
  7. L. Aravind (additional)
  8. Juha-Pekka Pursiheimo (additional)
  9. Shalini Oberdoerffer (additional)
  10. X. Shirley Liu (additional)
  11. Riitta Lahesmaa (additional)
  12. Harri Lähdesmäki (additional)
  13. Anjana Rao (additional)
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Dates
Type When
Created 12 years, 11 months ago (Sept. 19, 2012, 4:03 a.m.)
Deposited 2 years, 2 months ago (June 25, 2023, 5:35 p.m.)
Indexed 1 year, 2 months ago (June 7, 2024, 3:56 a.m.)
Issued 12 years, 11 months ago (Sept. 18, 2012)
Published 12 years, 11 months ago (Sept. 18, 2012)
Published Online 12 years, 11 months ago (Sept. 18, 2012)
Published Print 12 years, 11 months ago (Oct. 2, 2012)
Funders 0

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@article{Benson_2012, title={Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells}, volume={109}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1214414109}, DOI={10.1073/pnas.1214414109}, number={40}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Benson, Micah J. and Äijö, Tarmo and Chang, Xing and Gagnon, John and Pape, Utz J. and Anantharaman, Vivek and Aravind, L. and Pursiheimo, Juha-Pekka and Oberdoerffer, Shalini and Liu, X. Shirley and Lahesmaa, Riitta and Lähdesmäki, Harri and Rao, Anjana}, year={2012}, month=sep, pages={16252–16257} }