Prp24: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Kara Perdue, Michal Harel, Alexander Berchansky

@@ Line 46: / Line 46: @@
 Prp24 is part of the normal U6 snRNP, along with seven Lsm proteins.  After interaction with the U4 snRNP to form the U4/U6 di-snRNP, Prp24 departs from the di-snRNP before the addition of U5 to form the tri-snRNP U4/U6.U5 (reference!!).  Through many studies, it has been shown that Prp24 interacts extensively with specific sites on U6, as well with the Lsm protein ring on the 3' terminal end of the U6 snRNA.
-=== U6 snRNA ===
+=== U6 snRNA and U4/U6 snRNP ===
 U6 is arguably the most structurally dynamic snRNA involved in the splicing process, seemingly undergoing at least three different structures: it exists in one conformation as free U6 snRNP, another when base paired in the U4/U6 di-snRNP, and a third in base pairing interactions with U2 and the 5' splice site.  One large role suggested for Prp24 has been in assisting in the conformational changes between the free U6 structure and the U4/U6 conformation.
@@ Line 52: / Line 52: @@
 Prp24 coimmunoprecipitates with free U6 from solution, as well as with U4/U6 (reference Shannon and Guthrie 1991, Ghetti et al. 1995).  Initial investigation revealed that Prp24 binds within the 30-56 nucleotide region of free U6, as well as to stem II of U4/U6 in the 39-56 and 67-70 nucleotide regions of U6 (reference Ghetti et al. 1995).  Further investigation of the structure showed that Prp24 very likely binds directly to the 40-43 nucleotides of U6 based on chemical modification of naked U6 snRNA compared to free U6 snRNP (reference Jandrositz and Guthrie 1995).
-There are varied interactions between U6 and Prp24, as is evidenced by the suppression of temperature sensitive mutations in U6 by mutations in Prp24.  Mutations in RRM 2 and RRM 3 suppress the effects of mutations in the 3' stem of U6, in a region termed the telestem (reference Vidaver et al. 1999) (the existence of the telestem has been challenged by recent U6 secondary structure models (reference Karaduman et al. 2006/8 and Dunn and Rader 2010)).
+The interactions of Prp24 with U6 and U4/U6 are very important in proper spliceosome assembly, as evidenced by mutations in Prp24 that suppress mutations in U6 or U4.  Mutations in RRM 2 and RRM 3 suppress the effects of mutations in the 3' stem of U6, in a region termed the telestem (reference Vidaver et al. 1999) (the existence of the telestem has been challenged by recent U6 secondary structure models (reference Karaduman et al. 2008 and Dunn and Rader 2010)).  A later study showed that RRM 1 binds with high affinity to U6 and is important in interactions with mutations in the 3' region of U6 (reference Kwan and Brow 2005).  Mutations in two RNP consensus domains of Prp24 suppress the effects of mutations in U4 in the stem II region of U4/U6 (reference Shannon and Guthrie 1991).  Truncation and deletion of internal segments of U6 showed that the central region of U6 is the most important region for interaction with Prp24 and that RRM 1 and RRM 2 are the likely portions of Prp24 that interact with U6 in this region (reference Kwan and Brow 2005).
+NMR analysis of fragments of U6 sequence and regions of Prp24 have further defined and supported the interactions of the protein with U6 snRNA.  Analysis of an RNA oligonucleotide containing sequences identical to nucleotides 41-46 and 83-88 of U6 (the regions proposed to bind to Prp24) with a truncated protein containing RRMs 1 and 2 of Prp24 showed that these RRMs interacted sequence specifically with these nucleotides (Bae et al. 2008).
 === Lsm Proteins ===