How Selenocysteine (Sec) Is Incorporated into Proteins During Translation

Selenocysteine (Sec) is known as the 21st amino acid and is uniquely incorporated into proteins during translation. Unlike the standard 20 amino acids, Sec incorporation requires a specialized mechanism because it is encoded by what is normally a stop codon (UGA).

Mechanism of Selenocysteine Incorporation

• Charging and Modification:
  Selenocysteine is not directly charged onto a unique tRNA initially. Instead, serine is first charged onto a specialized tRNA called tRNA^Sec. This tRNA is distinct from the regular tRNA^Ser.

• Conversion of Serine to Selenocysteine:
  After charging, the serine attached to tRNA^Sec is enzymatically converted into selenocysteine while still bound to the tRNA.

• Incorporation at UGA Codon:
  The UGA codon, which normally signals translation termination, is recoded to incorporate Sec instead. This recoding requires a selenocysteine insertion sequence (SECIS) element in the mRNA and specialized protein factors such as Sec insertion sequence binding protein 2 (SBP2) and a Sec-specific elongation factor (eEFSec).

• Delivery to Ribosome:
  The Sec-tRNA^Sec complex is delivered to the ribosomal A site at the UGA codon, allowing Sec to be incorporated into the growing polypeptide chain.

Explanation of the Options

Summary

Selenocysteine incorporation is a unique co-translational process involving:

• Charging of serine onto tRNA^Sec

• Enzymatic conversion of serine to selenocysteine on the tRNA

• Recognition of the UGA stop codon as a Sec codon facilitated by the SECIS element and specialized factors

• Incorporation of Sec into the polypeptide chain at the UGA codon site

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Conclusion

The incorporation of selenocysteine into proteins occurs by charging serine onto a specialized tRNA^Sec, followed by enzymatic modification of the serine to selenocysteine. This Sec-tRNA^Sec is then incorporated at a UGA codon recoded as a Sec codon through the action of SECIS elements and specific elongation factors. Therefore, the correct answer is:

(4) charging of serine into tRNA^Sec followed by modification of serine into selenocysteine and then incorporation through a specially placed stop codon