Section 3: Genetics, Cellular and Molecular Biology
Classical Genetics and Epistasis
Subtopic: Mendelian Genetics & Gene Interactions
Question Statement:
5 capping of mRNA transcripts in eukaryotes involves the following events:
P. Addition of GMP on the 5 end
Q. Removal of -phosphate of the triphosphate on first base at the 5 end
R. 5-5 linkage between GMP and the first base at 5 end
S. Addition of methyl group to N7 position of guanine
Which one of the following is the correct sequence of events?
Options:
(A) P, Q, R, S
(B) P, R, Q, S
(C) Q, P, R, S
(D) Q, P, S, R
Official Answer Key:
C
Step-by-Step Solution & Explanation
### **Official Solution & Step-by-Step Derivation (GATE BT 2018 Q.50)**
**1. Governing Concept & Question Classification**:
- **Section**: BT
- **Question Type**: **MCQ** (2 Marks)
- **Topic**: Molecular Biology (Eukaryotic mRNA Post-Transcriptional Capping Mechanism)
**2. Detailed Step-by-Step Derivation**:
- In eukaryotes, the 5′ $m^7G$ cap structure is added co-transcriptionally to nascent pre-mRNA when the transcript reaches 20–30 nucleotides in length.
- The enzymatic reaction sequence proceeds via three tightly coordinated steps:
1. **Step 1 (RNA triphosphatase)**: Cleaves and removes the $\gamma$-phosphate from the 5′-triphosphate terminus of the first nascent nucleotide, leaving a 5′-diphosphate:
$5' ext{-pppNp}\cdots \xrightarrow{ ext{RNA triphosphatase}} 5' ext{-ppNp}\cdots + ext{P}_i \quad ext{[Event Q]}$
2. **Step 2 (Guanylyltransferase)**: Transfers a GMP moiety from GTP to the 5′-diphosphate end, forming an unusual $5' ext{--}5'$ triphosphate linkage with the release of inorganic pyrophosphate ($PP_i$):
$5' ext{-ppNp}\cdots + ext{GTP} \xrightarrow{ ext{Guanylyltransferase}} 5' ext{-G(5')ppp(5')Np}\cdots + PP_i \quad ext{[Events P and R]}$
3. **Step 3 (Guanine-N7 methyltransferase)**: Transfers a methyl group from S-adenosylmethionine (SAM) to the $N^7$ position of the terminal guanine base to yield the functional cap 0 structure ($m^7GpppNp\dots$):
$ ext{[Event S]}$
- Therefore, the correct chronological sequence is:
$ ext{Q} o ext{P} o ext{R} o ext{S}$
- **Option-by-Option Evaluation**:
- **Option (A) [INCORRECT]**: Omits the initial removal of the $\gamma$-phosphate (Q must precede P).
- **Option (B) [INCORRECT]**: Places Q after R.
- **Option (C) [CORRECT]**: Q (removal of $\gamma$-phosphate) $ o$ P (addition of GMP) $ o$ R ($5' o 5'$ triphosphate linkage formation) $ o$ S (methylation at N7 position of guanine).
- **Option (D) [INCORRECT]**: Places methylation (S) before $5' ext{--}5'$ linkage completion.
**3. Final Answer / Verification Summary**:
- **Official GATE Answer Key**: **C**
- **Scoring Criteria**: +2.0 Marks (Negative marking: -0.67 marks).
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