Heterogeneous ribonucleoprotein particle

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). The presence of the proteins bound to a pre-mRNA molecule serves as a signal that the pre-mRNA is not yet fully processed and therefore not ready for export to the cytoplasm.[1] Since most mature RNA is exported from the nucleus relatively quickly, most RNA-binding protein in the nucleus exist as heterogeneous ribonucleoprotein particles. After splicing has occurred, the proteins remain bound to spliced introns and target them for degradation.

hnRNPs are also integral to the 40S subunit of the ribosome and therefore important for the translation of mRNA in the cytoplasm.[2] However, hnRNPs also have their own nuclear localization sequences (NLS) and are therefore found mainly in the nucleus. Though it is known that a few hnRNPs shuttle between the cytoplasm and nucleus, immunofluorescence microscopy with hnRNP-specific antibodies shows nucleoplasmic localization of these proteins with little staining in the nucleolus or cytoplasm.[3] This is likely because of its major role in binding to newly transcribed RNAs. High-resolution immunoelectron microscopy has shown that hnRNPs localize predominantly to the border regions of chromatin, where it has access to these nascent RNAs.[4]

The proteins involved in the hnRNP complexes are collectively known as heterogeneous ribonucleoproteins. They include protein K and polypyrimidine tract-binding protein (PTB), which is regulated by phosphorylation catalyzed by protein kinase A and is responsible for suppressing RNA splicing at a particular exon by blocking access of the spliceosome to the polypyrimidine tract.[5]: 326  hnRNPs are also responsible for strengthening and inhibiting splice sites by making such sites more or less accessible to the spliceosome.[6] Cooperative interactions between attached hnRNPs may encourage certain splicing combinations while inhibiting others.[7]

  1. ^ Kinniburgh, A. J.; Martin, T. E. (1976-08-01). "Detection of mRNA sequences in nuclear 30S ribonucleoprotein subcomplexes". Proceedings of the National Academy of Sciences. 73 (8): 2725–2729. Bibcode:1976PNAS...73.2725K. doi:10.1073/pnas.73.8.2725. ISSN 0027-8424. PMC 430721. PMID 1066686.
  2. ^ Beyer, Ann L.; Christensen, Mark E.; Walker, Barbara W.; LeStourgeon, Wallace M. (1977). "Identification and characterization of the packaging proteins of core 40S hnRNP particles". Cell. 11 (1): 127–138. doi:10.1016/0092-8674(77)90323-3. PMID 872217. S2CID 41245800.
  3. ^ Dreyfuss, Gideon; Matunis, Michael J.; Pinol-Roma, Serafin; Burd, Christopher G. (1993-06-01). "hnRNP Proteins and the Biogenesis of mRNA". Annual Review of Biochemistry. 62 (1): 289–321. doi:10.1146/annurev.bi.62.070193.001445. ISSN 0066-4154. PMID 8352591.
  4. ^ Fakan, S.; Leser, G.; Martin, T. E. (January 1984). "Ultrastructural distribution of nuclear ribonucleoproteins as visualized by immunocytochemistry on thin sections". The Journal of Cell Biology. 98 (1): 358–363. doi:10.1083/jcb.98.1.358. ISSN 0021-9525. PMC 2113018. PMID 6231300.
  5. ^ Matsudaira PT, Lodish HF, Berk A, Kaiser C, Krieger M, Scott MP, Bretscher A, Ploegh H (2008). Molecular cell biology. San Francisco: W.H. Freeman. ISBN 978-0-7167-7601-7.
  6. ^ Matlin, Arianne J.; Clark, Francis; Smith, Christopher W. J. (2005). "Understanding alternative splicing: towards a cellular code". Nature Reviews Molecular Cell Biology. 6 (5): 386–398. doi:10.1038/nrm1645. ISSN 1471-0080. PMID 15956978. S2CID 14883495.
  7. ^ Martinez-Contreras, Rebeca; Cloutier, Philippe; Shkreta, Lulzim; Fisette, Jean-François; Revil, Timothée; Chabot, Benoit (2007). "HNRNP Proteins and Splicing Control". Alternative Splicing in the Postgenomic Era. Advances in Experimental Medicine and Biology. Vol. 623. pp. 123–147. doi:10.1007/978-0-387-77374-2_8. ISBN 978-0-387-77373-5. ISSN 0065-2598. PMID 18380344.