Biology Reference
In-Depth Information
Table 2, continued
MCTS
Transition IDs
T-Invariant IDs
Biological Interpretation
ID
ID
#
%
ID
#
%
18
t99, t100
2
1.24
i44-i71
28 39.44 Prp16 induced and slowed ATP
hydrolysis and commitment of C-
complex to discard pathway, dis-
assembly supported by hPrp43
19
t130-t132
3
1.86
i15-i20, i27-i32, i50-i55, i62-
i67
24 33.80 TIA1 intron binding
Σ - 127 78.86 - - - -
Each MCTS comprises reactions that are exclusively shared by several T-invariants and hence describe frequently used routes
through the spliceosomal assembly network.
Decomposition of the spliceosomal network into functional units
Analysis of maximal common transition sets
Maximal common transition sets (MCTS) have been defined as a more generalized concept of enzyme
subsets, which define enzymes in a biochemical network that operate under steady state conditions always
together, in one or several different metabolic fluxes. Enzyme subsets further require that the enzymes
involved are all regulated in the same direction and that their fluxes behave proportional [Pfeiffer et al. ,
1999]. MCTS, in contrast, are based on the support of T-invariants, and, thus, do not take stoichiometric
relations into consideration. Due to missing stoichiometric coefficients the constraint of proportionality
does not apply. They describe sets of reactions that are exclusively in a maximal number of T-invariants
(“signaling fluxes”) present, hence, being shared by different signaling pathways. MCTS and the places
and arcs in between form disjunctive subnetworks and can be interpreted as functional building blocks.
Given the correctness or biological meaning of T-invariants, MCTS emphasize key parts of signaling
routes and facilitate the description of functional parts of a network. Vice versa , they can indicate
modeling flaws if they combine transitions without proven biological relationship.
Table 2 summarizes the computed MCTS. There exist six smaller MCTS composed of only
two transitions, which nevertheless represent crucial elements of the assembly pathway. MCTS 1
( t0.U2AF35 3ss bdg , t1.3ss in ) describes the recognition of the 3'ss by the factor U2AF35, which oc-
curs in more than 56% of all T-invariants. Next frequently, MCTS 7 is formed by two reactions shared
by 32 T-invariants (45%), which describe the influx of the bridging factor FBP11 ( t15.FBP11 in ) and
subsequent binding of the U2 snRNP to the branch site t24.U2 BPS bdg1 ). Taken together, MCTS 4
and MCTS 7 form a subpathway that covers the FBP11 supported interaction of U1 snRNP with the
branch point bound factor SF1 and the subsequent joining and structural rearrangement of U2 snRNP
with replacement of U2AF at the polypyrimidin tract. The remaining small MCTS still occurs in more
than one quarter of all invariant pathways and cover the NTC-complex and Prp19 integration (MCTS
16), the late SF3b125 action in 17S U2 maturation (MCTS 9), and the slowed ATP hydolysis by Prp16
with initiation of the discard pathway (MCTS 18).
The largest shared transition set (MCTS 2) covers 54/161 (33%) of all transitions, which are part of more
than three quarter of all T-invariants. This MCTS represents a fundamental building block that defines
biological functions at essential stages of spliceosome assembly, for example, branch point definition,
15S U2 snRNP assembly, SF3a and SF3b subcomplex formation, U5- and U6 snRNP maturation and
the cyclophilin trimer formation. The energy supply by ATP and removal of ADP is part of MCTS
2, which naturally has to be shared by many T-invariants because each stage requires ATP either for
phosphorylation or hydrolyzation reactions.
The maturation and recycling of the U1 and U4 snRNP
 
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