**13. Does tyrosine phosphorylation of a RNA polymerase subunit favour its dissociation from the core enzyme?**

The two models presented here (figures 6 and 7) make an attempt to find an explanation for the observations mentioned above.

(1) Gene (2) RNA polymerase (3) RNA polymerase subunit that is recognized by naER (4) naER (5) E-RAF (6) estradiol-17β (7) spliceosome (8) nERII (9) RNA polymerase subunit phosphorylated by nERII (10) other subunits dissociated from the RNA polymerase (11) RNA (12) Nuclear pore complex (13) Nucleus (14) cytoplasm.

Fig. 6. naER-nERII transformation during post transcriptional control of gene expression.

No Yes

20 30

The factor responsible for this transformation was subsequently found to be a 61kDa protein, the naER

Table 1. **Comparison of molecular properties associated with naER and nER II of the goat** 

**13. Does tyrosine phosphorylation of a RNA polymerase subunit favour its** 

The two models presented here (figures 6 and 7) make an attempt to find an explanation for

(1) Gene (2) RNA polymerase (3) RNA polymerase subunit that is recognized by naER (4) naER (5) E-RAF (6) estradiol-17β (7) spliceosome (8) nERII (9) RNA polymerase subunit phosphorylated by nERII (10) other subunits dissociated from the RNA polymerase (11) RNA (12) Nuclear pore complex (13)

Fig. 6. naER-nERII transformation during post transcriptional control of gene expression.

Insensitive to estradiol

exposure

 naER nERII Sedimentation Value 4.6S 3.7S Stokes radius 36A0 23 A0 Glycoprotein nature Yes No

estradiol

Dimerisation with E-RAF Yes No

Tyrosine kinase activity Sensitive to exposure to

Interaction with Hsp-90 in the

transforming factor (Jaya & Thampan,2000).

**dissociation from the core enzyme?** 

the observations mentioned above.

Nucleus (14) cytoplasm.

presence of estradiol

**uterus** 

nM estradiol needed for saturation binding

The figure on the left displays the interaction of naER-E-RAF heterodimer with genetic elements. While E-RAF recognizes the DNA, naER binds to nuclear RNA polymerase subunits. The figure on the right is a spliceosome -set -up in which the nERII –RNA complex is shown in association with subunits dissociated from RNA polymerase.

nERII is a RNA binding estrogen receptor. Whether naER-E-RAF heterodimer has its binding site on the target gene different from those of the ERα/ERβ mediated gene regulation or whether the action of the heterodimer is independent of the classical estrogen receptor function remains to be clarified. The binding site on the estrogen responsive target gene for E-RAF-naER heterodimer has not yet been identified while there is every likelihood to suggest that it will be different from the estrogen responsive element(ERE).A candidate site could well be AP-1 site in view of an earlier observation that c-fos and E-RAF share immunological similarity. While E-RAF binds to the gene, naER interacts with the nuclear RNA polymerases. Possibly, the naER to nERII transformation could be an event that takes place at the end of the transcription process initiated by the heterodimer. At this stage, nERII dissociates from E-RAF and binds to the RNA (rRNA/mRNA/5S rRNA/tRNA). I wish to propose here that the phosphorylated subunits of the RNA polymerases might dissociate from the core enzyme and move along with nERII during the succeeding stages of gene regulation that witness splicing, nucleocytoplasmic transport and translation.

Sebastian and Thampan (2002 a,b)and Sebastian et al(2004) presented some fascinating observations in this context. Goat uterine nERII was found to be associated with ribonucleoproteins containing U-1 and U-2 snRNA's. Within the snRNP framework nERII interacted with three proteins with molecular masses 32kDa, 55kDa and 60kDa.While p55 and p60 were found to be RNA binding proteins, p32 was found to be involved only in protein-protein interactions with nERII. Whether this protein is the same as SC35 reported by Parnaik in the context of spliceosome assembly (Tripathi & Parnaik,2008) remains to be seen. It was interesting to observe that nERII in association with p32 and p55 formed an effective Ca++/Mg++ activated ATPase that appeared to be directly involved in the nucleocytoplasmic movement of RNP.

(1) nERII (2) rRNA (3) RNA polymerase I subunit(4)40S ribosomal subunit(5)60S ribosomal subunit.
