+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

MRNA maturation by two-step trans-splicing/polyadenylation processing in trypanosomes



MRNA maturation by two-step trans-splicing/polyadenylation processing in trypanosomes



Proceedings of the National Academy of Sciences of the United States of America 104(7): 2035-2042



Trypanosomes are unique eukaryotic cells, in that they virtually lack mechanisms to control gene expression at the transcriptional level. These microorganisms mostly control protein synthesis by posttranscriptional regulation processes, like mRNA stabilization and degradation. Transcription in these cells is polycistronic. Tens to hundreds of protein-coding genes of unrelated function are arrayed in long clusters on the same DNA strand. Polycistrons are cotranscriptionally processed by trans-splicing at the 5' end and polyadenylation at the 3' end, generating monocistronic units ready for degradation or translation. In this work, we show that some trans-splicing/polyadenylation sites may be skipped during normal polycistronic processing. As a consequence, dicistronic units or monocistronic transcripts having long 3' UTRs are produced. Interestingly, these unspliced transcripts can be processed into mature mRNAs by the conventional trans-splicing/polyadenylation events leading to translation. To our knowledge, this is a previously undescribed mRNA maturation by trans-splicing uncoupled from transcription. We identified an RNA-recognition motif-type protein, homologous to the mammalian polypyrimidine tract-binding protein, interacting with one of the partially processed RNAs analyzed here that might be involved in exon skipping. We propose that splice-site skipping might be part of a posttranscriptional mechanism to regulate gene expression in trypanosomes, through the generation of premature nontranslatable RNA molecules.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 013033457

Download citation: RISBibTeXText

PMID: 17267594

DOI: 10.1073/pnas.0611125104


Related references

A common pyrimidine-rich motif governs trans-splicing and polyadenylation of tubulin polycistronic pre-mRNA in trypanosomes. Genes and Development 8(4): 491-501, 1994

Temporal order of RNA-processing reactions in trypanosomes: rapid trans splicing precedes polyadenylation of newly synthesized tubulin transcripts. Molecular and Cellular Biology 13(1): 720-725, 1993

Trypanosoma brucei: a preferential splicing at the inverted polyadenylation site of the VSG mRNA provides further evidence for coupling between trans-splicing and polyadenylation. Experimental Parasitology 80(3): 563-567, 1995

MRNA maturation by two-step trans-splicing. Proceedings of the National Academy of Sciences of the United States of America13 104(7): 2035-2042, 2007

Mitochondrial Polyadenylation Is a One-Step Process Required for mRNA Integrity and tRNA Maturation. Plos Genetics 12(5): E1006028, 2016

Reciprocal effects of splicing and polyadenylation on human immunodeficiency virus type 1 pre-mRNA processing. Virology 224(2): 498-509, 1996

Erythroid-specific processing of human beta spectrin I pre-mRNA Competition between alternative polyadenylation and splicing. Experimental Hematology (charlottesville). 22(8): 840, 1994

Heat-shock disruption of trans-splicing in trypanosomes: effect on Hsp70, Hsp85 and tubulin mRNA synthesis. Gene 82(1): 169-175, 1989

Erythroid-specific alternative processing of human beta spectrin I pre-mRNA Competition between polyadenylation and splicing pathways. Clinical Research 42(3): 405A, 1994

Polycistronic pre-mRNA processing in vitro: snRNP and pre-mRNA role reversal in trans-splicing. Genes and Development 24(15): 1645-1658, 2010

Trans mRNA splicing in trypanosomes: cloning and analysis of a PRP8-homologous gene from Trypanosoma brucei provides evidence for a U5-analogous RNP. Embo Journal 16(14): 4433-4440, 1997

Widespread mRNA polyadenylation events in introns indicate dynamic interplay between polyadenylation and splicing. Genome Research 17(2): 156-165, 2007

Trans-complementation of the second step of pre-mRNA splicing by exogenous 5' exons. Rna 5(7): 876-882, 1999

Cis-splicing and polyadenylation of actin RNA can precede 5' trans-splicing in nematodes. Biochemical and Biophysical Research Communications 211(1): 49-53, 1995