also contribute to regulation, as it is involved in recruitment of some critical components in the formation of the hairpin. Structure In intrinsic termination, the RNA transcript doubles back and base pairs with itself, creating an RNA stem-loop, or hairpin, structure. This structure is critical for the release of both the transcript and polymerase at the end of transcription. In living cells, the key components are the stable stem-loop itself, as well as the sequence of 6-8 uracil residues that follow it. The stem usually consists of 8-9 mostly guanine and cytosine (G-C) base pairs, and the loop consists of 4-8 residues. It is thought that the stem portion of the structure is essential for transcription termination, while the loop is not. This is suggested by the fact that termination can be achieved in non-native structures that do not include the loop. The stem portion of the hairpin is usually rich in G-C base pairs. G-C base pairs have significant base-stacking interactions, and can form three hydrogen bonds with each other, which makes them very thermodynamically favorable. Conversely, while the uracil-rich sequence that follows the hairpin is not always necessary for termination, it is hypothesized that the uracil-rich sequence aids in intrinsic termination because the U-A bond is not as strong as G-C bonds. This inherent instability acts to kinetically favor the dissociation of the RNA transcript. Experiments to determine structurally significant features To determine the optimal length of the stem, researchers modified its length and observed how quickly termination occurred. When the length of the stem was lengthened or shortened from the standard 8-9 base pair length, termination was less efficient, and if the changes were great enough, termination ceased completely. Experiments determined that if an oligonucleotide sequence that is identical to the downstream portion of the stem is present, it will base pair with the upstream portion. This creates a structure that is analogous to the native stem-loop structure but is missing the loop at the end. Without the presence of the loop, intrinsic termination is still able to occur. This indicates that the loop is not inherently necessary for intrinsic termination. Generally, the absence of the uracil-rich sequence following the stem-loop will result in a delay or pause in transcription, but termination will not cease completely. Mechanism Intrinsic termination is cued by signals directly encoded in the DNA and RNA. Signal appears in as a hairpin and