U4 spliceosomal RNA

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U4 spliceosomal RNA
GO
GO:0017070 GO:0000353 GO:0000351 GO:0005687 GO:0046540
SOSO:0000393
PDB structuresPDBe
A 3D representation of a fragment of a U4 snRNA. The crystal structure of the spliceosomal 15.5KD protein is bound to a U4 snRNA fragment.[1]

The U4 small nuclear Ribo-Nucleic Acid (U4 snRNA) is a

mRNA). It forms a duplex with U6, and with each splicing round, it is displaced from the U6 snRNA (and the spliceosome) in an ATP-dependent manner, allowing U6 to re-fold and create the active site for splicing catalysis. A recycling process involving protein Brr2 releases U4 from U6, while protein Prp24 re-anneals U4 and U6. The crystal structure of a 5′ stem-loop of U4 in complex with a binding protein has been solved.[1]

Biological role

The U4 snRNA has been shown to exist in a number of different formats including: bound to proteins as a small nuclear Ribo-Nuclear Protein snRNP,[2] involved with the U6 snRNA in the di-snRNP,[3] as well as involved with both the U6 snRNA and the U5 snRNA in the tri-snRNP.[4][5] The different formats have been proposed to coincide with different temporal events in the activity of the penta-snRNP,[6] or as intermediates in the step-wise model of spliceosome assembly and activity.[7]

The U4 snRNA (and its likely analog snR14 in Yeast[8]) has been shown not to participate directly in the specific catalytic activities of the splicing reaction,[9] and is proposed instead to act as a regulator of the U6 snRNA. The U4 snRNA inhibits spliceosome activity during assembly by complementary base pairing between the U6 snRNA in two highly conserved stem regions.[10] It is suggested that this base-pairing interaction prevents the U6 snRNA from assembling with the U2 snRNA into the conformation required for catalytic activity.[11] If the U4 snRNA is degraded and thereby removed from the spliceosome, splicing is effectively halted.[12] The U4 and U6 snRNAs are demonstratively required for splicing in vitro.[13]

Structure

Figure 1. Naked U4 putative secondary structure.
Figure 2. Putative U4/U6 base pairing secondary structure.

The U4 snRNA secondary structure is suggested to alter depending on its interaction with the U6 snRNA.

RNA structure probing[16] indicate that U4 snRNA secondary structure contains several conserved motifs,[17] which serve structural as well as intermediary roles in establishing interactions with other splicing components. The putative U4/U6 snRNA base pairing secondary structure shown in Figure 2., is conserved across a diverse set of organisms suggesting the splicing machinery's ancient origins.[18] It has been shown previously that a highly conserved Kinked-loop participates in specific protein interactions.[1][19]

Interactions

The U4 snRNA must be displaced from U6 snRNA in an ATP dependent process involving the protein Brr2 - before the spliceosome is made active.

RNAse enzymes.[25][26] Over 100 proteins have been identified that participate in spliceosomal pathway, several proteins of varying size are also known to interact with the U4 snRNP.[27]

References

  1. ^
    PMID 11163207
    .
  2. S2CID 14302377
    .
  3. PMID 6204860
    .
  4. PMID 2552294
    .
  5. PMID 11720284
    .
  6. PMID 11804584
    .
  7. ^
    PMID 2962902
    .
  8. S2CID 9476222
    .
  9. ^
    PMID 1833635
    .
  10. PMID 2977088
    .
  11. S2CID 6407709
    .
  12. S2CID 44660539
    .
  13. S2CID 2899820
    .
  14. PMID 10322216
    .
  15. PMID 12384583
    .
  16. PMID 11955014
    .
  17. PMID 10644672
    .
  18. PMID 16818600
    .
  19. PMID 16373487
    .
  20. S2CID 45969803
    .
  21. ^
    PMID 9452384
    .
  22. PMID 8299941
    .
  23. PMID 7882985
    .
  24. PMID 7585243
    .
  25. PMID 11226169
    .
  26. S2CID 4421636
    .
  27. PMID 12374753
    .

Further reading

External links
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