Disease relevance of RN7SL1

• Some RNAs were underrepresented, with ratios relative to 7SL several orders of magnitude lower in virions than in cells, while others displayed intermediate values [1].
• Upstream sequences from the 7SL RNA gene, U6 RNA gene, vault RNA gene, and BC1 gene increase transcription of Alu, B2 and BC1 in transient transfections of NIH3T3, HeLa, Neuro2a and C6 glioma cell lines [2].
• Novel autoantibodies against 7SL RNA in patients with polymyositis/dermatomyositis [3].
• These results also show that in addition to the abundant 7SL, 4.5S and 4.5S1 RNAs having homology to repetitive DNA, Novikoff hepatoma cells also contain several minor small RNAs with homology to repetitive sequences [4].

High impact information on RN7SL1

• We have cloned and sequenced a cDNA copy of in vitro-polyadenylated 7SL RNA of HeLa cells [5].
• Why then does RNA polymerase III transcribe the few 7SL genes so efficiently, while transcripts from the far more abundant Alu elements are not readily detectable [6]?
• We find that a human 7SL gene and a synthetic Alu sequence derived from it are expressed 50-100-fold more efficiently in vitro than either a representative Alu element or two 7SL pseudogenes [6].
• The human genome is rich in sequences which are structurally related to the 7SL RNA component of the signal recognition particle [6].
• 5' Deletion and insertion mutants of the 7SL gene demonstrate that, in conjunction with the internal promoter, the first 37 nucleotides upstream from the transcription start site are essential for efficient and accurate initiation in vitro [6].

Biological context of RN7SL1

• Human genes and pseudogenes for the 7SL RNA component of signal recognition particle [7].
• All are truncated copies of 7SL RNA, but the site of truncation can occur at either the 5' end, the 3' end or at both ends of the RNA sequence [7].
• This shows that the M-domain contains an RNA binding site, and suggests that SRP54 may be linked to the rest of SRP through this domain by a direct interaction with 7SL RNA [8].
• Each monomer of the dimeric Alu element shares sequence homology with the 7SL RNA component of the signal recognition particle (SRP) [9].
• We suggest that the genomic sequences upstream from most Alu elements and 7SL pseudogenes do not contain this element, and consequently that only a small subset of such sequences can be transcribed in vivo [6].

Anatomical context of RN7SL1

• 2. The 7L30.2 locus differs by several single base changes from the known human 7SL RNA sequences and does not appear to be expressed at a detectable level in HeLa cells [7].
• Mammalian signal recognition particle (SRP), a complex of six polypeptides and one 7SL RNA molecule, is required for targeting nascent presecretory proteins to the endoplasmic reticulum (ER) [10].
• SRP19 synthesized in a cell-free system specifically bound to 7SL RNA [11].
• Decreasing sensitivity to chemical modification between these different substrates suggests regions on 7SL RNA that: bind proteins associated with SRP might interact with ribosomes; and are protected by binding to membranes [12].
• The structure of 7SL RNA has been probed by chemical modification followed by primer extension, using four substrates: (i) naked 7SL RNA; (ii) free signal recognition particle (SRP); (iii) polysome bound SRP; and (iv) membrane bound SRP [12].

Associations of RN7SL1 with chemical compounds

• Sucrose density gradient studies confirmed that this protein co-migrated with the 7SL RNA, indicating the likelihood that it is physically associated with this RNA [13].
• Analysis of 7SL RNA labeled in this in vitro adenylation system showed that a single adenylic acid residue is added to the 3'-end [14].
• The human 7SL RNA component of the signal recognition particle can be separated into four major conformers by nondenaturing polyacrylamide gel electrophoresis [15].
• A region of homology with the upstream sequences of the genes for U6 RNA, 7SL RNA and Bombyx mori alanine tRNA is found within 50 bp from the transcription start point [16].
• These results suggest that the human Alu family was generated from the 7SL RNA by deletion, insertion, and mutations, which thus modified the ancestral 7SL sequence so that it could form a structure more closely resembling lysine tRNA [17].

Physical interactions of RN7SL1

• We have determined the crystal structure of Methanococcus jannaschii SRP19 bound to the S domain of human 7SL RNA at 2.9 A resolution [18].

Other interactions of RN7SL1

• Here we present the crystal structure of a human SRP ternary complex consisting of SRP19, the M domain of SRP54 and the S domain of 7SL RNA [19].
• The binding of SRP54 to the S domain of 7SL RNA is highly dependent on SRP19 [19].
• We also report the isolation and characterisation of a human genomic clone carrying two linked 7SL RNA coding regions, 7L30.1 and 7L30 [7].
• In particular, we argue that two of the loci are secondary 7SL pseudogenes which derive from RNA polymerase III transcripts of primary (preexisting) 7SL pseudogenes [7].

Analytical, diagnostic and therapeutic context of RN7SL1

• Sequence analysis of the RNAs indicated a single base difference between the conformers at position 133 (C in 7SL II and U in 7SL I) located in domain III [20].
• Insertion of the tetranucleotide GAGA, which is an important region of the second promoter for RNA polymerase III in the Alu sequence, occurred during the deletion and ligation process to generate the Alu sequence from the parental 7SL RNA [17].
• Southern blot analysis of hop DNA revealed 12 7SL-specific signals corresponding to HindIII fragments ranging from 0.45 to 7.8 kb [21].
• In addition, 7SL and U1 RNAs were identified by northern blot hybridization to cloned human and sea urchin probes, respectively [22].
• RESULTS: The immunoprecipitation analysis indicated that 5 Japanese (50%) and one North American (5%) patient with anti-SRP antibodies had novel autoantibodies against deproteinized 7SL RNA [3].

References