cancer. During times of cellular glucose restriction, AMP-activated protein kinase (AMPK) discourages metabolic processes that consume energy but are non-essential. As a result, it is capable of phosphorylating RNA polymerase I (at the Ser-635 site) in order to down-regulate rRNA synthesis by disrupting transcription initiation. Impairment or removal of more than one pseudouridine or 29-O-methylation regions from the ribosome decoding center significantly reduces rate of rRNA transcription by reducing the rate of incorporation of new amino acids. Formation of heterochromatin is essential to silencing rRNA transcription, without which ribosomal RNA is synthesized unchecked and greatly decreases the lifespan of the organism. In prokaryotes Similar to eukaryotes, the production of rRNA is the rate-limiting step in the prokaryotic synthesis of a ribosome. In E. coli, it has been found that rRNA is transcribed from the two promoters P1 and P2 found within seven different rrn operons. The P1 promoter is specifically responsible for regulating rRNA synthesis during moderate to high bacterial growth rates. Because the transcriptional activity of this promoter is directly proportional to the growth rate, it is primarily responsible for rRNA regulation. An increased rRNA concentration serves as a negative feedback mechanism to ribosome synthesis. High NTP concentration has been found to be required for efficient transcription of the rrn P1 promoters. They are thought to form stabilizing complexes with RNA polymerase and the promoters. In bacteria specifically, this association of high NTP concentration with increased rRNA synthesis provides a molecular explanation as to why ribosomal and thus protein synthesis is dependent on growth-rate. A low growth-rate yields lower rRNA / ribosomal synthesis rates while a higher growth rate yields a higher rRNA / ribosomal synthesis rate. This allows a cell to save energy or increase its metabolic activity dependent on its needs and available resources. In prokaryotic cells, each rRNA gene or operon is transcribed into a single RNA precursor that includes 16S, 23S, 5S rRNA and tRNA sequences along with transcribed spacers. The RNA processing then begins before the transcription is complete. During processing reactions, the rRNAs and tRNAs are released as separate molecules. Prokaryotic regulation Because of the vital role rRNA plays in the cell physiology of prokaryotes, there is much overlap in rRNA regulation mechanisms. At the transcriptional level, there are both positive and negative effectors of rRNA transcription that facilitate a cell's maintenance of homeostasis: An UP element upstream of the rrn P1 promoter